Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand Breaks

被引：329

作者：

Moyal, Lilach ^{[1
]}

Lerenthal, Yaniv ^{[1
]}

Gana-Weisz, Mali ^{[1
]}

Mass, Gilad ^{[1
]}

So, Sairei ^{[2
]}

Wang, Shih-Ya ^{[2
]}

Eppink, Berina ^{[3
,4
]}

Chung, Young Min ^{[5
]}

Shalev, Gil ^{[1
]}

Shema, Efrat ^{[6
]}

Shkedy, Dganit ^{[1
]}

Smorodinsky, Nechama I. ^{[7
]}

van Vliet, Nicole ^{[3
,4
]}

Kuster, Bernhard ^{[8
]}

Mann, Matthias ^{[9
]}

Ciechanover, Aaron ^{[10
,11
]}

Dahm-Daphi, Jochen ^{[12
]}

Kanaar, Roland ^{[3
,4
]}

Hu, Mickey C. -T. ^{[5
]}

Chen, David J. ^{[2
]}

Oren, Moshe ^{[6
]}

Shiloh, Yosef ^{[1
]}

机构：

[1] Tel Aviv Univ, Sackler Sch Med, David & Inez Myers Lab Genet Res, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel

[2] Univ Texas SW Med Ctr Dallas, Div Mol Radiat Biol, Dept Radiat Oncol, Dallas, TX 75390 USA

[3] Erasmus MC, Dept Cell Biol & Genet, NL-3000 CA Rotterdam, Netherlands

[4] Erasmus MC, Canc Genom Ctr, Dept Radiat Oncol, NL-3000 CA Rotterdam, Netherlands

[5] Stanford Univ, Div Gynecol Oncol, Sch Med, Stanford, CA 94305 USA

[6] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

[7] Tel Aviv Univ, Alec & Myra Marmot Hybridoma Unit, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel

[8] Tech Univ Munich, Dept Prote & Bioanalyt, D-85354 Freising Weihenstephan, Germany

[9] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[10] Technion Israel Inst Technol, Rappaport Fac Med, Vasc & Tumor Biol Res Ctr, IL-31096 Haifa, Israel

[11] Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel

[12] Univ Med Ctr Hamburg Eppendorf, Lab Radiobiol & Expt Radiat Oncol, D-20246 Hamburg, Germany

来源：

MOLECULAR CELL | 2011年 / 41卷 / 05期

基金：

以色列科学基金会; 美国国家卫生研究院;

关键词：

MAMMALIAN-CELLS; DAMAGE RESPONSE; GENE-EXPRESSION; HOMOLOGOUS RECOMBINATION; ATAXIA-TELANGIECTASIA; CHECKPOINT RESPONSE; H3; METHYLATION; UBIQUITYLATION; UBIQUITINATION; PATHWAY;

D O I：

10.1016/j.molcel.2011.02.015

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 cellular response to DNA double-strand breaks (DSBs) is mobilized by the protein kinase ATM, which phosphorylates key players in the DNA damage response (DDR) network. A major question is how ATM controls DSB repair. Optimal repair requires chromatin relaxation at damaged sites. Chromatin reorganization is coupled to dynamic alterations in histone posttranslational modifications. Here, we show that in human cells, DSBs induce monoubiquitylation of histone H2B, a modification that is associated in undamaged cells with transcription elongation. We find that this process relies on recruitment to DSB sites and ATM-dependent phosphorylation of the responsible E3 ubiquitin ligase: the RNF20-RNF40 heterodimer. H2B monoubiquitylation is required for timely recruitment of players in the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair-and optimal repair via both pathways. Our data and previous data suggest a two-stage model for chromatin decondensation that facilitates DSB repair.

引用

页码：529 / 542

页数：14

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