生物
泛素
抄写(语言学)
复制因子C
DNA复制
细胞生物学
组蛋白
赖氨酸
原点识别复合体
复制前复合体
遗传学
染色体复制控制
真核细胞DNA复制
DNA
基因
语言学
哲学
氨基酸
作者
Shuailin Hao,Ya Wang,Yu-Qin Zhao,Wen Gao,Wei Cui,Youhang Li,Jian Cui,Yu Liu,Lixiu Lin,Xingzhi Xu,Hailong Wang
摘要
Abstract The reversible post-translational modification (PTM) of proteins plays an important role in many cellular processes. Lysine crotonylation (Kcr) is a newly identified PTM, but its functional significance remains unclear. Here, we found that Kcr is involved in the replication stress response. We show that crotonylation of histone H2A at lysine 119 (H2AK119) and ubiquitination of H2AK119 are reversibly regulated by replication stress. Decrotonylation of H2AK119 by SIRT1 is a prerequisite for subsequent ubiquitination of H2AK119 by BMI1. Accumulation of ubiquitinated H2AK119 at reversed replication forks leads to the release of RNA Polymerase II and transcription repression in the vicinity of stalled replication forks. These effects attenuate transcription–replication conflicts (TRCs) and TRC-associated R-loop formation and DNA double-strand breaks. These findings suggest that decrotonylation and ubiquitination of H2A at lysine 119 act together to resolve replication stress-induced TRCs and protect genome stability.
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