聚（ADP-核糖基）化在DNA损伤反应和癌症化疗中的作用。

The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy.

作者信息

Li M, Yu X

机构信息

1] Department of Obstetrics and Gynecology, Reproductive Medical Center, Peking University Third Hospital, Beijing, China [2] Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

出版信息

Oncogene. 2015 Jun;34(26):3349-56. doi: 10.1038/onc.2014.295. Epub 2014 Sep 15.

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 post-translational 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.

DNA损伤是一种有害威胁，但每天都会在所有类型的细胞中发生。作为对DNA损伤的反应，多聚（ADP-核糖）化，一种独特的翻译后修饰，会在DNA损伤处由多聚（ADP-核糖）聚合酶（PARP）立即催化，这有助于DNA损伤修复。最近的研究表明，多聚（ADP-核糖）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抑制剂对DNA损伤诱导的多聚（ADP-核糖）化的抑制会损害早期DNA损伤反应事件。此外，PARP抑制剂正在作为针对BRCA缺陷肿瘤的III期临床试验中的抗癌药物出现。在这篇综述中，我们讨论了关于DNA损伤反应中多聚（ADP-核糖）化的最新发现，以及PARP抑制剂选择性杀死具有BRCA突变的肿瘤细胞的分子机制。