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[聚(ADP - 核糖)聚合酶1作为DNA修复的关键调节因子]

[Poly(ADP-Ribose) polymerase 1 as a key regulator of DNA repair].

作者信息

Khodyreva S N, Lavrik O I

机构信息

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia.

出版信息

Mol Biol (Mosk). 2016 Jul-Aug;50(4):655-673. doi: 10.7868/S0026898416040030.

DOI:10.7868/S0026898416040030
PMID:27668604
Abstract

Poly(ADP-ribosyl)ation (PARylation) of proteins is one of the immediate cell responses to DNA damage and is catalyzed by poly(ADP-ribose) polymerases (PARPs). When bound to damaged DNA, some members of the PARP family are activated and use NAD^(+) as a source of ADP to catalyze synthesis of poly(ADP-ribose) (PAR) covalently attached to a target protein. PAR synthesis is considered as a mechanism that provides a local signal of DNA damage and modulates protein functions in response to genotoxic agents. PARP1 is the best-studied protein of the PARP family and is widely known аs a regulator of repair of damaged bases and single-strand nicks. Data are accumulating that PARP1 is additionally involved in double-strand break repair and nucleotide excision repair. The review summarizes the literature data on the role that PARP1 and PARylation play in DNA repair and particularly in base excision repair; original data obtained in our lab are considered in more detail.

摘要

蛋白质的多聚(ADP-核糖)化(PARylation)是细胞对DNA损伤的即时反应之一,由多聚(ADP-核糖)聚合酶(PARP)催化。当与受损DNA结合时,PARP家族的一些成员被激活,并利用NAD⁺作为ADP的来源,催化合成共价连接到靶蛋白上的多聚(ADP-核糖)(PAR)。PAR合成被认为是一种机制,可提供DNA损伤的局部信号,并响应基因毒性剂调节蛋白质功能。PARP1是PARP家族中研究最多的蛋白质,作为受损碱基和单链切口修复的调节剂而广为人知。越来越多的数据表明,PARP1还参与双链断裂修复和核苷酸切除修复。本文综述了关于PARP1和PARylation在DNA修复,特别是碱基切除修复中作用的文献数据;对我们实验室获得的原始数据进行了更详细的讨论。

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