DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A

被引:198
作者
Bergink, Steven
Salomons, Florian A.
Hoogstraten, Deborah
Groothuis, Tom A. M.
de Waard, Harm
Wu, Junxin
Yuan, Li
Citterio, Elisabetta
Houtsmuller, Adriaan B.
Neefjes, Jacques
Hoeijmakers, Ian H. J.
Vermeulen, Wim
Dantuma, Nico P. [1 ]
机构
[1] Karolinska Inst, Med Nobel Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
[2] Erasmus Med Ctr, Ctr Biomed Genet, MGC, Dept Cell Biol & Genet, NL-3015 GE Rotterdam, Netherlands
[3] Erasmus Med Ctr, Dept Pathol, NL-3015 GE Rotterdam, Netherlands
[4] IFOM, Ist FIRC Oncol Mol, I-20139 Milan, Italy
[5] Netherlands Canc Inst, Div Tumor Biol, NL-1066 CX Amsterdam, Netherlands
关键词
DNA repair; ubiquitin-proteasome system; histone; chromatin; ATR; H2AX; DNA damage response;
D O I
10.1101/gad.373706
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chromatin changes within the context of DNA repair remain largely obscure. Here we show that DNA damage induces monoubiquitylation of histone H2A in the vicinity of DNA lesions. Ultraviolet (UV)-induced monoubiquitylation of H2A is dependent on functional nucleotide excision repair and occurs after incision of the damaged strand. The ubiquitin ligase Ring2 is required for the DNA damage-induced H2A ubiquitylation. UV-induced ubiquitylation of H2A is dependent on the DNA damage signaling kinase ATR (ATM- and Rad3-related) but not the related kinase ATM (ataxia telangiectasia-mutated). Although the response coincides with phosphorylation of variant histone H2AX, H2AX was not required for H2A ubiquitylation. Together our data show that monoubiquitylation of H2A forms part of the cellular response to UV damage and suggest a role of this modification in DNA repair-induced chromatin remodeling.
引用
收藏
页码:1343 / 1352
页数:10
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