Regulation of Homologous Recombination by RNF20-Dependent H2B Ubiquitination

被引：295

作者：

Nakamura, Kyosuke ^{[1
]}

Kato, Akihiro ^{[1
]}

Kobayashi, Junya ^{[1
]}

Yanagihara, Hiromi ^{[1
]}

Sakamoto, Shuichi ^{[1
]}

Oliveira, Douglas V. N. P. ^{[1
]}

Shimada, Mikio ^{[1
]}

Tauchi, Hiroshi ^{[2
]}

Suzuki, Hidekazu ^{[3
]}

Tashiro, Satoshi ^{[3
]}

Zou, Lee ^{[4
]}

Komatsu, Kenshi ^{[1
]}

机构：

[1] Kyoto Univ, Ctr Radiat Biol, Sakyo Ku, Kyoto 6068501, Japan

[2] Ibaraki Univ, Dept Biol Sci, Mito, Ibaraki 3108512, Japan

[3] Hiroshima Univ, Res Inst Radiat Biol & Med, Minami Ku, Hiroshima 7348553, Japan

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA

来源：

MOLECULAR CELL | 2011年 / 41卷 / 05期

关键词：

CHROMATIN REMODELING COMPLEXES; DNA-DAMAGE RESPONSE; HISTONE H2B; DISTINCT ROLES; REPAIR; UBIQUITYLATION; TRANSCRIPTION; BRCA1; NBS1; ATM;

D O I：

10.1016/j.molcel.2011.02.002

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：

The E3 ubiquitin ligase RNF20 regulates chromatin structure by monoubiquitinating histone H2B in transcription. Here, we show that RNF20 is localized to double-stranded DNA breaks (DSBs) independently of H2AX and is required for the DSB-induced H2B ubiquitination. In addition, RNF20 is required for the methylation of H3K4 at DSBs and the recruitment of the chromatin-remodeling factor SNF2h. Depletion of RNF20, depletion of SNF2h, or expression of the H2B mutant lacking the ubiquitination site (K120R) compromises resection of DNA ends and recruitment of RAD51 and BRCA1. Consequently, cells lacking RNF20 or SNF2h and cells expressing H2B K120R exhibit pronounced defects in homologous recombination repair (HRR) and enhanced sensitivity to radiation. Finally, the function of RNF20 in HRR can be partially bypassed by forced chromatin relaxation. Thus, the RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling.

引用

页码：515 / 528

页数：14

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