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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

MRN complex is an essential effector of DNA damage repair

Abstract: Genome stability can be threatened by both endogenous and exogenous agents. Organisms have evolved numerous mechanisms to repair DNA damage, including homologous recombination (HR) and non-homologous end joining (NHEJ). Among the factors associated with DNA repair, the MRE11-RAD50-NBS1 (MRN) complex (MRE11-RAD50-XRS2 in Saccharomyces cerevisiae) plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair. Upon detecting DNA damage, the MRN complex activates signaling molecules, such as the protein kinase ataxia-telangiectasia mutated (ATM), to trigger a broad DNA damage response, including cell cycle arrest. The nuclease activity of the MRN complex is responsible for DNA end resection, which guides DNA repair to HR in the presence of sister chromatids. The MRN complex is also involved in NHEJ, and has a species-specific role in hairpin repair. This review focuses on the structure of the MRN complex and its function in DNA damage repair.

Key words: DNA damage repair; MRE11-RAD50-NBS1 (MRN) complex; Homologous recombination; Non-homologous end joining

Chinese Summary  <24> MRN蛋白复合物是一个重要的DNA损伤修复效应因子

概要:基因组的稳定性时刻都遭受着来自细胞内源和外源损伤因素的威胁,如果这些损伤不能够被及时、准确地修复,将会导致细胞衰老、死亡,甚至癌变的发生。因此,为了维持基因组稳定性,生物体进化出了一系列复杂而精确的修复方式以应对DNA损伤,包括同源重组修复和非同源末端连接修复。其中,MRE11-RAD50-NBS1(MRN)复合物(酿酒酵母同源物为MRE11-RAD50-XRS2)不仅参与DNA损伤识别和信号传递,还在同源重组修复和非同源末端连接修复过程中发挥着极其重要的作用。当DNA损伤被识别后,MRN复合物首先会激活信号分子(如ATM激酶等),从而引发信号级联反应放大DNA损伤应答效应,包括细胞周期阻滞。作为一个核酸酶,MRN复合物利用其核酸酶活性进行DNA末端切割,在有姐妹染色单体存在时,促使同源重组修复。此外,MRN复合物也参与了非同源末端连接修复,并在修复发卡结构方面具有物种特异性。该篇综述将主要讨论MRN复合物的结构及其在DNA损伤修复中的功能。

关键词组:DNA损伤修复;MRE11-RAD50-NBS1(MRN)蛋白复合物;同源重组修复;非同源末端连接修复


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DOI:

10.1631/jzus.B2000289

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On-line Access:

2021-01-15

Received:

2020-06-01

Revision Accepted:

2020-08-16

Crosschecked:

2020-12-16

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