A Role for Small RNAs in DNA Double-Strand Break Repair

被引：483

作者：

Wei, Wei ^{[1
,2
,3
]}

Ba, Zhaoqing ^{[1
,4
]}

Gao, Min ^{[5
]}

Wu, Yang ^{[1
]}

Ma, Yanting ^{[1
]}

Amiard, Simon ^{[6
]}

White, Charles I. ^{[6
]}

Danielsen, Jannie Michaela Rendtlew ^{[5
,7
]}

Yang, Yun-Gui ^{[5
]}

Qi, Yijun ^{[1
,8
,9
]}

机构：

[1] Nat Inst Biol Sci, Beijing 102206, Peoples R China

[2] Chinese Acad Med Sci, Grad Program, Beijing 100730, Peoples R China

[3] Peking Union Med Coll, Beijing 100730, Peoples R China

[4] Beijing Normal Univ, Coll Life Sci, Beijing 100875, Peoples R China

[5] Chinese Acad Sci, Beijing Inst Genom, Dis Genom & Individualized Med Lab, Genome Struct & Stabil Grp, Beijing 100029, Peoples R China

[6] Clermont Univ, Inst Natl Sante & Rech Med U931, Ctr Natl Rech Sci, Unite Mixte Rech 6247, F-63177 Aubiere, France

[7] Novo Nordisk Fdn Ctr Prot Res, Fac Hlth Sci, Ubiquitin Signalling Grp, DK-2200 Copenhagen, Denmark

[8] Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China

[9] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

来源：

CELL | 2012年 / 149卷 / 01期

关键词：

TRANS-ACTING SIRNAS; HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; DIFFERENT PATHWAYS; STRUCTURAL BASIS; ATR; RECOGNITION; METHYLATION; GAMMA-H2AX; MECHANISMS;

D O I：

10.1016/j.cell.2012.03.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Eukaryotes have evolved complex mechanisms to repair DNA double-strand breaks (DSBs) through coordinated actions of protein sensors, transducers, and effectors. Here we show that similar to 21-nucleotide small RNAs are produced from the sequences in the vicinity of DSB sites in Arabidopsis and in human cells. We refer to these as diRNAs for DSB-induced small RNAs. In Arabidopsis, the biogenesis of diRNAs requires the PI3 kinase ATR, RNA polymerase IV (Pol IV), and Dicer-like proteins. Mutations in these proteins as well as in Pol V cause significant reduction in DSB repair efficiency. In Arabidopsis, diRNAs are recruited by Argonaute 2 (AGO2) to mediate DSB repair. Knock down of Dicer or Ago2 in human cells reduces DSB repair. Our findings reveal a conserved function for small RNAs in the DSB repair pathway. We propose that diRNAs may function as guide molecules directing chromatin modifications or the recruitment of protein complexes to DSB sites to facilitate repair.

引用

页码：101 / 112

页数：12

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