Poly(ADP-ribose) polymerase (PARP-1) in homologous recombination and as a target for cancer therapy
Poly(ADP-ribose) polymerase (PARP-1) in homologous recombination and as a target for cancer therapy
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DOI：
10.4161/cc.4.9.2031
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发表时间：
2005-09-01
期刊：
影响因子：
4.3
通讯作者：
Schultz, N
中科院分区：
文献类型：
--
作者：
Helleday, T;Bryant, HE;Schultz, N
多聚（ADP - 核糖）聚合酶（PARP - 1）与DNA断裂位点结合以促进DNA修复。然而，PARP - 1在DNA修复中的作用似乎并非至关重要，因为PARP - 1基因敲除小鼠能够存活、具有生育能力，且不会过早形成肿瘤。从这些小鼠中分离出的细胞显示出同源重组水平升高。同源重组与PARP - 1之间存在复杂的联系，并且PARP - 1在DNA双链断裂修复中可能具有一定作用。尽管PARP - 1对于同源重组本身似乎并非必需，但它通过参与DNA单链断裂（SSB）的修复来调控这一过程。持续到细胞周期S期的单链断裂会使复制叉瓦解，从而触发同源重组以重新启动复制。我们讨论了近期关于使用PARP - 1抑制剂作为针对重组缺陷型癌症（如BRCA2肿瘤）的靶向癌症治疗的相关发现。
Poly( ADP-ribose) polymerase (PARP-1) binds to DNA breaks to facilitate DNA repair. However, the role of PARP-1 in DNA repair appears to not be critical since PARP-1 knockout mice are viable, fertile and do not develop early onset tumors. Cells isolated from these mice show an increased level of homologous recombination. There is an intricate link between homologous recombination and PARP-1 and a possible role for PARP-1 in DNA double-strand break repair. Although PARP-1 appears not to be required for homologous recombination itself, it regulates the process through its involvement in the repair of DNA single-strand breaks (SSBs). SSBs persisting into the S phase of the cell cycle collapse replication forks, triggering homologous recombination for replication restart. We discuss the recent discoveries on the use of PARP-1 inhibitors as a targeted cancer therapy for recombination deficient cancers, such as BRCA2 tumors.