ATM-mediated KDM2A phosphorylation is required for the DNA damage repair

doi:10.1038/onc.2015.81

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	ATM-mediated KDM2A phosphorylation is required for the DNA damage repair
	Cao, L-L ; Wei, F. ; Du, Y. ; Song, B. ; Wang, D. ; Shen, C. ; Lu, X. ; Cao, Z. ; Yang, Q. ; Gao, Y. ; Wang, L. ; Zhao, Y. ; Wang, H. ; Yang, Y. ; Zhu, W-G
刊名	ONCOGENE
	2016
关键词	DOUBLE-STRAND BREAKS HISTONE H3 MRE11-RAD50-NBS1 COMPLEX HOMOLOGOUS RECOMBINATION CELLULAR-RESPONSE GENOTOXIC STRESS MRE11 COMPLEX SITES DEMETHYLASE METHYLATION
DOI	10.1038/onc.2015.81
英文摘要	The ataxia-telangiectasia mutated (ATM) protein is a key signaling molecule that modulates the DNA damage response. However, the exact mechanism by which ATM regulates DNA damage repair has not yet been elucidated. Here, we report that ATM regulates the DNA damage response by phosphorylating lysine-specific demethylase 2A (KDM2A), a histone demethylase that acts at sites of H3K36 dimethylation. ATM interacts with KDM2A, and their interaction significantly increases in response to DNA double-stranded, but not single-stranded, breaks. ATM specifically phosphorylates KDM2A at threonine 632 (T632) following DNA damage, as demonstrated by a mutagenesis assay and mass spectrometric analysis. Although KDM2A phosphorylation does not alter its own demethylase activity, T632 phosphorylation of KDM2A largely abrogates its chromatin-binding capacity, and H3K36 dimethylation near DNA damage sites is significantly increased. Consequently, enriched H3K36 dimethylation serves as a platform to recruit the MRE11 complex to DNA damage sites by directly interacting with the BRCT2 domain of NBS1, which results in efficient DNA damage repair and enhanced cell survival. Collectively, our study reveals a novel mechanism for ATM in connecting histone modifications with the DNA damage response.; National Key Basic Research Program of China [2011CB504200, 2013CB911000]; National Natural Science Foundation of China [31070691, 81321003, 91319302]; Minister of Education of China '111 Project'; SCI(E); ARTICLE; zhuweiguo@bjmu.edu.cn; 3; 301-313; 35
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/438777]
专题	生命科学学院
推荐引用方式 GB/T 7714	Cao, L-L,Wei, F.,Du, Y.,et al. ATM-mediated KDM2A phosphorylation is required for the DNA damage repair[J]. ONCOGENE,2016.
APA	Cao, L-L.,Wei, F..,Du, Y..,Song, B..,Wang, D..,...&Zhu, W-G.(2016).ATM-mediated KDM2A phosphorylation is required for the DNA damage repair.ONCOGENE.
MLA	Cao, L-L,et al."ATM-mediated KDM2A phosphorylation is required for the DNA damage repair".ONCOGENE (2016).