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 Jan H J, Vermeulen Wim, Dantuma Nico P
MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Genes Dev. 2006 May 15;20(10):1343-52. doi: 10.1101/gad.373706.
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.
在DNA修复过程中的染色质变化在很大程度上仍不清楚。在此我们表明,DNA损伤会在DNA损伤位点附近诱导组蛋白H2A发生单泛素化。紫外线(UV)诱导的H2A单泛素化依赖于功能性核苷酸切除修复,且发生在损伤链切口之后。泛素连接酶Ring2是DNA损伤诱导的H2A泛素化所必需的。UV诱导的H2A泛素化依赖于DNA损伤信号激酶ATR(ATM和Rad3相关),而不依赖于相关激酶ATM(共济失调毛细血管扩张症突变型)。尽管该反应与变异组蛋白H2AX的磷酸化同时发生,但H2AX对于H2A泛素化并非必需。我们的数据共同表明,H2A的单泛素化构成了细胞对UV损伤反应的一部分,并提示这种修饰在DNA修复诱导的染色质重塑中发挥作用。