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GLP-catalyzed H4K16me1 promotes 53BP1 recruitment to permit DNA damage repair and cell survival.


ABSTRACT: The binding of p53-binding protein 1 (53BP1) to damaged chromatin is a critical event in non-homologous DNA end joining (NHEJ)-mediated DNA damage repair. Although several molecular pathways explaining how 53BP1 binds damaged chromatin have been described, the precise underlying mechanisms are still unclear. Here we report that a newly identified H4K16 monomethylation (H4K16me1) mark is involved in 53BP1 binding activity in the DNA damage response (DDR). During the DDR, H4K16me1 rapidly increases as a result of catalyzation by the histone methyltransferase G9a-like protein (GLP). H4K16me1 shows an increased interaction level with 53BP1, which is important for the timely recruitment of 53BP1 to DNA double-strand breaks. Differing from H4K16 acetylation, H4K16me1 enhances the 53BP1-H4K20me2 interaction at damaged chromatin. Consistently, GLP knockdown markedly attenuates 53BP1 foci formation, leading to impaired NHEJ-mediated repair and decreased cell survival. Together, these data support a novel axis of the DNA damage repair pathway based on H4K16me1 catalysis by GLP, which promotes 53BP1 recruitment to permit NHEJ-mediated DNA damage repair.

SUBMITTER: Lu X 

PROVIDER: S-EPMC6868394 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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GLP-catalyzed H4K16me1 promotes 53BP1 recruitment to permit DNA damage repair and cell survival.

Lu Xiaopeng X   Tang Ming M   Zhu Qian Q   Yang Qiaoyan Q   Li Zhiming Z   Bao Yantao Y   Liu Ge G   Hou Tianyun T   Lv Yafei Y   Zhao Ying Y   Wang Haiying H   Yang Yang Y   Cheng Zhongyi Z   Wen He H   Liu Baohua B   Xu Xingzhi X   Gu Luo L   Zhu Wei-Guo WG  

Nucleic acids research 20191201 21


The binding of p53-binding protein 1 (53BP1) to damaged chromatin is a critical event in non-homologous DNA end joining (NHEJ)-mediated DNA damage repair. Although several molecular pathways explaining how 53BP1 binds damaged chromatin have been described, the precise underlying mechanisms are still unclear. Here we report that a newly identified H4K16 monomethylation (H4K16me1) mark is involved in 53BP1 binding activity in the DNA damage response (DDR). During the DDR, H4K16me1 rapidly increase  ...[more]

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