|
|
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = -;code = 45
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
result sql = Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents.
Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents.char = U;code = 85
char = V;code = 86
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = R;code = 82
char = );code = 41
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = k;code = 107
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = F;code = 70
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = l;code = 108
char = j;code = 106
char = u;code = 117
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = S;code = 83
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = 8;code = 56
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 9;code = 57
char = ;;code = 59
char = ;code = 32
char = F;code = 70
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = l;code = 108
char = j;code = 106
char = u;code = 117
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = N;code = 78
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = 4;code = 52
char = 1;code = 49
char = 0;code = 48
char = ,;code = 44
char = ;code = 32
char = 8;code = 56
char = 4;code = 52
char = 2;code = 50
char = -;code = 45
char = 8;code = 56
char = 4;code = 52
char = 7;code = 55
char = );code = 41
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = F;code = 70
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = l;code = 108
char = j;code = 106
char = u;code = 117
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = S;code = 83
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = 8;code = 56
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 9;code = 57
char = );code = 41
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = R;code = 82
char = /;code = 47
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = -;code = 45
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = l;code = 108
char = e;code = 101
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = s;code = 115
char = p;code = 112
char = e;code = 101
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char = i;code = 105
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char = a;code = 97
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char = t;code = 116
char = h;code = 104
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char = d;code = 100
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char = A;code = 65
char = ;code = 32
char = i;code = 105
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char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
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char = g;code = 103
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = o;code = 111
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char = e;code = 101
char = o;code = 111
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char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = o;code = 111
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char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
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char = s;code = 115
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char = r;code = 114
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char = s;code = 115
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char = t;code = 116
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char = h;code = 104
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char = 1;code = 49
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char = d;code = 100
char = e;code = 101
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char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
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char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = o;code = 111
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char = e;code = 101
char = r;code = 114
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = o;code = 111
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char = o;code = 111
char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = /;code = 47
char = C;code = 67
char = d;code = 100
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = H;code = 72
char = E;code = 69
char = S;code = 83
char = E;code = 69
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = S;code = 83
char = U;code = 85
char = G;code = 71
char = G;code = 71
char = E;code = 69
char = S;code = 83
char = T;code = 84
char = ;code = 32
char = T;code = 84
char = H;code = 72
char = A;code = 65
char = T;code = 84
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = (;code = 40
char = a;code = 97
char = );code = 41
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = /;code = 47
char = M;code = 77
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = G;code = 71
char = 1;code = 49
char = /;code = 47
char = S;code = 83
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = (;code = 40
char = b;code = 98
char = );code = 41
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = k;code = 107
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = k;code = 107
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = UV and ionizing radiation (IR) activate DNA damage checkpoints and induce Cdc25A degradation (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J., and Lukas, J. (2000) Science 288, 1425-1429; Falck, J., Mailand, N., Syljuasen, R. G., Bartek, J., and Lukas J. (2001) Nature 410, 842-847). The degradation of Cdc25A is abrogated by caffeine, which implicates Chk1 as the potential mediator (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J., and Lukas, J. (2000) Science 288, 1425-1429). However, the involvement of Chk1 is far from clear, because caffeine is a rather nonspecific inhibitor of the ATR/Chk1 signaling pathway. Additionally, it is not known whether DNA-damaging drugs commonly used in chemotherapy, which may activate different signal transduction pathways than UV or IR, also confer Cdc25A degradation. Herein, we show that camptothecin and doxorubicin, two widely used topoisomerase inhibitors conferring S and G2 arrest, respectively, cause the degradation of Cdc25A. Using a small interfering RNA that enables the specific elimination of Chk1 expression, we show that the observed proteolysis of Cdc25A is mediated through Chk1. Moreover, Cdc25A overexpression abrogates the Chk1-mediated degradation and overcomes the doxorubicin-induced G2 arrest through dephosphorylation and activation of Cdc2/Cdk1 in a dose-dependent manner. THESE RESULTS SUGGEST THAT: (a) Cdc25A is involved in the G2/M transition in addition to its commonly accepted effect on G1/S progression, and (b) Chk1 mediates both S and G2 checkpoint and is thus a more ubiquitous cell cycle checkpoint mediator than previously thought.
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char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = -;code = 45
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
result sql = Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents.
char = V;code = 86
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = R;code = 82
char = );code = 41
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = k;code = 107
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = F;code = 70
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = l;code = 108
char = j;code = 106
char = u;code = 117
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = S;code = 83
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = 8;code = 56
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 9;code = 57
char = ;;code = 59
char = ;code = 32
char = F;code = 70
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = l;code = 108
char = j;code = 106
char = u;code = 117
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = N;code = 78
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = 4;code = 52
char = 1;code = 49
char = 0;code = 48
char = ,;code = 44
char = ;code = 32
char = 8;code = 56
char = 4;code = 52
char = 2;code = 50
char = -;code = 45
char = 8;code = 56
char = 4;code = 52
char = 7;code = 55
char = );code = 41
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = F;code = 70
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = y;code = 121
char = l;code = 108
char = j;code = 106
char = u;code = 117
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = l;code = 108
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = k;code = 107
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = L;code = 76
char = u;code = 117
char = k;code = 107
char = a;code = 97
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = .;code = 46
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = S;code = 83
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = 8;code = 56
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = 9;code = 57
char = );code = 41
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = A;code = 65
char = T;code = 84
char = R;code = 82
char = /;code = 47
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = -;code = 45
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = U;code = 85
char = V;code = 86
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = U;code = 85
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = /;code = 47
char = C;code = 67
char = d;code = 100
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = H;code = 72
char = E;code = 69
char = S;code = 83
char = E;code = 69
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = S;code = 83
char = U;code = 85
char = G;code = 71
char = G;code = 71
char = E;code = 69
char = S;code = 83
char = T;code = 84
char = ;code = 32
char = T;code = 84
char = H;code = 72
char = A;code = 65
char = T;code = 84
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = (;code = 40
char = a;code = 97
char = );code = 41
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = c;code = 99
char = 2;code = 50
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = /;code = 47
char = M;code = 77
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = G;code = 71
char = 1;code = 49
char = /;code = 47
char = S;code = 83
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = (;code = 40
char = b;code = 98
char = );code = 41
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = k;code = 107
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = 2;code = 50
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = k;code = 107
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = q;code = 113
char = u;code = 117
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = k;code = 107
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = UV and ionizing radiation (IR) activate DNA damage checkpoints and induce Cdc25A degradation (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J., and Lukas, J. (2000) Science 288, 1425-1429; Falck, J., Mailand, N., Syljuasen, R. G., Bartek, J., and Lukas J. (2001) Nature 410, 842-847). The degradation of Cdc25A is abrogated by caffeine, which implicates Chk1 as the potential mediator (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J., and Lukas, J. (2000) Science 288, 1425-1429). However, the involvement of Chk1 is far from clear, because caffeine is a rather nonspecific inhibitor of the ATR/Chk1 signaling pathway. Additionally, it is not known whether DNA-damaging drugs commonly used in chemotherapy, which may activate different signal transduction pathways than UV or IR, also confer Cdc25A degradation. Herein, we show that camptothecin and doxorubicin, two widely used topoisomerase inhibitors conferring S and G2 arrest, respectively, cause the degradation of Cdc25A. Using a small interfering RNA that enables the specific elimination of Chk1 expression, we show that the observed proteolysis of Cdc25A is mediated through Chk1. Moreover, Cdc25A overexpression abrogates the Chk1-mediated degradation and overcomes the doxorubicin-induced G2 arrest through dephosphorylation and activation of Cdc2/Cdk1 in a dose-dependent manner. THESE RESULTS SUGGEST THAT: (a) Cdc25A is involved in the G2/M transition in addition to its commonly accepted effect on G1/S progression, and (b) Chk1 mediates both S and G2 checkpoint and is thus a more ubiquitous cell cycle checkpoint mediator than previously thought.
Publication: J. Biol. Chem. 2003 Jun 13 ;278(24)::21767-73.
Publication Date: 2003 Jun 13
Study Author(s): Xiao, Zhan;Chen, Zehan;Gunasekera, Angelo H;Sowin, Thomas J;Rosenberg, Saul H;Fesik, Steve;Zhang, Haiying;
Institution: Cancer Research, Abbott Laboratories, Abbott Park, Illinois 60064-6101, USA. [email protected]
Shortcut link to this study:
Publication Date: 2003 Jun 13
Study Author(s): Xiao, Zhan;Chen, Zehan;Gunasekera, Angelo H;Sowin, Thomas J;Rosenberg, Saul H;Fesik, Steve;Zhang, Haiying;
Institution: Cancer Research, Abbott Laboratories, Abbott Park, Illinois 60064-6101, USA. [email protected]
Shortcut link to this study:
UV and ionizing radiation (IR) activate DNA damage checkpoints and induce Cdc25A degradation (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J., and Lukas, J. (2000) Science 288, 1425-1429; Falck, J., Mailand, N., Syljuasen, R. G., Bartek, J., and Lukas J. (2001) Nature 410, 842-847). The degradation of Cdc25A is abrogated by caffeine, which implicates Chk1 as the potential mediator (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J., and Lukas, J. (2000) Science 288, 1425-1429). However, the involvement of Chk1 is far from clear, because caffeine is a rather nonspecific inhibitor of the ATR/Chk1 signaling pathway. Additionally, it is not known whether DNA-damaging drugs commonly used in chemotherapy, which may activate different signal transduction pathways than UV or IR, also confer Cdc25A degradation. Herein, we show that camptothecin and doxorubicin, two widely used topoisomerase inhibitors conferring S and G2 arrest, respectively, cause the degradation of Cdc25A. Using a small interfering RNA that enables the specific elimination of Chk1 expression, we show that the observed proteolysis of Cdc25A is mediated through Chk1. Moreover, Cdc25A overexpression abrogates the Chk1-mediated degradation and overcomes the doxorubicin-induced G2 arrest through dephosphorylation and activation of Cdc2/Cdk1 in a dose-dependent manner. THESE RESULTS SUGGEST THAT: (a) Cdc25A is involved in the G2/M transition in addition to its commonly accepted effect on G1/S progression, and (b) Chk1 mediates both S and G2 checkpoint and is thus a more ubiquitous cell cycle checkpoint mediator than previously thought.
PMID: 12676925
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