Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures

被引:218
作者
Clouaire, Thomas [1 ]
Rocher, Vincent [1 ]
Lashgari, Anahita [2 ]
Arnould, Coline [1 ]
Aguirrebengoa, Marion [1 ]
Biernacka, Anna [3 ]
Skrzypczak, Magdalena [3 ]
Aymard, Francois [1 ]
Fongang, Bernard [4 ]
Dojer, Norbert [4 ,5 ]
Iacovoni, Jason S. [6 ,7 ]
Rowicka, Maga [4 ]
Ginalski, Krzysztof [3 ]
Cote, Jacques [2 ]
Legube, Gaelle [1 ]
机构
[1] Univ Toulouse, UT3, CNRS, LBCMCP,CBI, F-31062 Toulouse, France
[2] Univ Laval, Res Ctr, St Patrick Res Grp Basic Oncol, Canc Res Ctr,Oncol Axis,CHU Quebec, Quebec City, PQ G1R 3S3, Canada
[3] Univ Warsaw, Ctr New Technol, Lab Bioinformat & Syst Biol, Zwirki i Wigury Warsaw 93, PL-02089 Warsaw, Poland
[4] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA
[5] Univ Warsaw, Inst Informat, Banacha 2, PL-02097 Warsaw, Poland
[6] INSERM, Bioinformat Plateau I2MC, F-31062 Toulouse, France
[7] Univ Toulouse, F-31062 Toulouse, France
基金
欧洲研究理事会; 加拿大健康研究院;
关键词
PROMOTES HOMOLOGOUS RECOMBINATION; GENOMIC INSTABILITY; H2B UBIQUITYLATION; DAMAGE RESPONSE; GENE-REGULATION; CELL-CYCLE; 53BP1; PHOSPHORYLATION; TRANSCRIPTION; ACETYLATION;
D O I
10.1016/j.molcel.2018.08.020
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
Double-strand breaks (DSBs) are extremely detrimental DNA lesions that can lead to cancer-driving mutations and translocations. Non-homologous end joining (NHEJ) and homologous recombination (HR) represent the two main repair pathways operating in the context of chromatin to ensure genome stability. Despite extensive efforts, our knowledge of DSB-induced chromatin still remains fragmented. Here, we describe the distribution of 20 chromatin features at multiple DSBs spread throughout the human genome using ChIP-seq. We provide the most comprehensive picture of the chromatin landscape set up at DSBs and identify NHEJ-and HR-specific chromatin events. This study revealed the existence of a DSB-induced monoubiquitination-to-acetylation switch on histone H2B lysine 120, likely mediated by the SAGA complex, as well as higher-order signaling at HR-repaired DSBs whereby histone H1 is evicted while ubiquitin and 53BP1 accumulate over the entire gH2AX domains.
引用
收藏
页码:250 / +
页数:19
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