Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition.
Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition.
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DOI：
10.1186/1471-2199-8-29
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发表时间：
2007-04-25
影响因子：
--
通讯作者：
Oliver FJ
中科院分区：
文献类型：
--
作者：
Aguilar-Quesada R;Muñoz-Gámez JA;Martín-Oliva D;Peralta A;Valenzuela MT;Matínez-Romero R;Quiles-Pérez R;Menissier-de Murcia J;de Murcia G;Ruiz de Almodóvar M;Oliver FJ
ATM和PARP-1是细胞对DNA损伤反应中最重要的两个参与者。PARP-1和ATM识别并结合单链和双链DNA断裂，以响应不同的触发。在这里，我们报告了ATM和PARP-1在体内未受损细胞中形成分子复合物，并且这种关联在γ辐射后增加。ATM在DNA损伤过程中也被PARP-1修饰。我们还评估了PARP-1缺失或抑制对ATM-激酶活性的影响，并发现尽管PARP-1缺陷细胞显示出缺陷的ATM-激酶活性和响应于γ-辐射的γ-H2 AX灶形成减少，但PARP抑制本身能够激活ATM-激酶。PARP抑制以ATM依赖性方式诱导γ H2 AX灶积聚。PARP的抑制也诱导DNA双链断裂，这依赖于ATM的存在。因此，ATM缺陷型细胞显示出对PARP抑制的敏感性增加。总之，我们的结果表明，虽然PARP-1是需要在ATM的γ射线照射的反应，抑制PARP诱导DNA双链断裂（这是解决和ATM依赖性途径），并激活ATM激酶。
ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after γ-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM-kinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced γ-H2AX foci formation in response to γ-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced γ H2AX foci accumulation, in an ATM-dependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase.
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影响因子：
8.8
作者：
Ramsay, J;Birrell, G;Baumann, K;Bodero, A;Parsons, P;Lavin, M
通讯作者：
Lavin, M
影响因子：
4.3
作者：
Helleday, T;Bryant, HE;Schultz, N
通讯作者：
Schultz, N
DOI：
10.1073/pnas.93.23.13084
发表时间：
1996-11-12
影响因子：
11.1
作者：
Elson, A;Wang, YQ;Leder, P
通讯作者：
Leder, P
影响因子：
1.7
作者：
LITTLE, JB;UENO, AM;DAHLBERG, WK
通讯作者：
DAHLBERG, WK
影响因子：
8
作者：
Valenzuela, MT;Guerrero, R;Oliver, FJ
通讯作者：
Oliver, FJ