The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy.
The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy.
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DNA损伤是一种有害的威胁，但每天都发生在所有类型的细胞中。为了应对DNA损伤，聚（ADP-核糖基）化是一种独特的翻译后修饰，它立即被DNA损伤处的聚（ADP-核糖）聚合酶（PARP）催化，从而促进DNA损伤修复。最近的研究表明，聚（ADP-核糖基）化是细胞DNA损伤反应的第一步之一，并控制早期DNA损伤反应途径。PARP抑制剂抑制DNA损伤诱导的聚（ADP-核糖基）化损害早期DNA损伤反应事件。此外，PARP抑制剂正在成为BRCA缺陷肿瘤III期临床试验中的抗癌药物。本文就聚ADP核糖基化在DNA损伤反应中的作用以及PARP抑制剂选择性杀伤BRCA突变肿瘤细胞的分子机制作一综述。
DNA damage is a deleterious threat, but occurs daily in all types of cells. In response to DNA damage, poly(ADP-ribosyl)ation, a unique posttranslational modification, is immediately catalyzed by poly(ADP-ribose) polymerases (PARPs) at DNA lesions, which facilitates DNA damage repair. Recent studies suggest that poly(ADP-ribosyl)ation is one of the first steps of cellular DNA damage response and governs early DNA damage response pathways. Suppression of DNA damage-induced poly(ADP-ribosyl)ation by PARP inhibitors impairs early DNA damage response events. Moreover, PARP inhibitors are emerging as anti-cancer drugs in phase III clinical trials for BRCA-deficient tumors. In this review, we discuss recent findings on poly(ADP-ribosyl)ation in DNA damage response as well as the molecular mechanism by which PARP inhibitors selectively kill tumor cells with BRCA mutations.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
4.4
作者：
Chapman, John D.;Gagne, Jean-Philippe;Goodett, David R.
通讯作者：
Goodett, David R.
影响因子：
64.8
作者：
Ahel, Ivan;Ahel, Dragana;West, Stephen C.
通讯作者：
West, Stephen C.
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ
DOI：
10.1016/0921-8777(89)90012-8
发表时间：
1989-09-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
ALVAREZGONZALEZ, R;ALTHAUS, FR
通讯作者：
ALTHAUS, FR