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Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress

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...

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Detalles Bibliográficos
Autores principales: Hao, Shuailin, Wang, Ya, Zhao, Yuqin, Gao, Wen, Cui, Wei, Li, Youhang, Cui, Jian, Liu, Yu, Lin, Lixiu, Xu, Xingzhi, Wang, Hailong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508856/
https://www.ncbi.nlm.nih.gov/pubmed/36062559
http://dx.doi.org/10.1093/nar/gkac734
Descripción
Sumario: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.