异染色质
异染色质蛋白1
细胞生物学
DNA修复
生物
DNA
常染色质
遗传学
分子生物学
染色质
作者
Lei Zhang,Xinran Geng,Fangfang Wang,Jinshan Tang,I. Yu,Arishya Sharma,Sora Jin,Mingyue Chen,Mingliang Tang,Franklin Mayca Pozo,Wenxiu Wang,Janet Wang,Michal Wozniak,Xiaoxia Guo,Masaru Miyagi,Fulai Jin,Yongjie Xu,Xin‐Sheng Yao,Youwei Zhang
标识
DOI:10.1038/s41467-022-28019-y
摘要
Human 53BP1 is primarily known as a key player in regulating DNA double strand break (DSB) repair choice; however, its involvement in other biological process is less well understood. Here, we report a previously uncharacterized function of 53BP1 at heterochromatin, where it undergoes liquid-liquid phase separation (LLPS) with the heterochromatin protein HP1α in a mutually dependent manner. Deletion of 53BP1 results in a reduction in heterochromatin centers and the de-repression of heterochromatic tandem repetitive DNA. We identify domains and residues of 53BP1 required for its LLPS, which overlap with, but are distinct from, those involved in DSB repair. Further, 53BP1 mutants deficient in DSB repair, but proficient in LLPS, rescue heterochromatin de-repression and protect cells from stress-induced DNA damage and senescence. Our study suggests that in addition to DSB repair modulation, 53BP1 contributes to the maintenance of heterochromatin integrity and genome stability through LLPS.
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