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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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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
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author Hao, Shuailin
Wang, Ya
Zhao, Yuqin
Gao, Wen
Cui, Wei
Li, Youhang
Cui, Jian
Liu, Yu
Lin, Lixiu
Xu, Xingzhi
Wang, Hailong
author_facet Hao, Shuailin
Wang, Ya
Zhao, Yuqin
Gao, Wen
Cui, Wei
Li, Youhang
Cui, Jian
Liu, Yu
Lin, Lixiu
Xu, Xingzhi
Wang, Hailong
author_sort Hao, Shuailin
collection PubMed
description 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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spelling pubmed-95088562022-09-26 Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress Hao, Shuailin Wang, Ya Zhao, Yuqin Gao, Wen Cui, Wei Li, Youhang Cui, Jian Liu, Yu Lin, Lixiu Xu, Xingzhi Wang, Hailong Nucleic Acids Res Genome Integrity, Repair and Replication 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. Oxford University Press 2022-09-05 /pmc/articles/PMC9508856/ /pubmed/36062559 http://dx.doi.org/10.1093/nar/gkac734 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genome Integrity, Repair and Replication
Hao, Shuailin
Wang, Ya
Zhao, Yuqin
Gao, Wen
Cui, Wei
Li, Youhang
Cui, Jian
Liu, Yu
Lin, Lixiu
Xu, Xingzhi
Wang, Hailong
Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress
title Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress
title_full Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress
title_fullStr Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress
title_full_unstemmed Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress
title_short Dynamic switching of crotonylation to ubiquitination of H2A at lysine 119 attenuates transcription–replication conflicts caused by replication stress
title_sort dynamic switching of crotonylation to ubiquitination of h2a at lysine 119 attenuates transcription–replication conflicts caused by replication stress
topic Genome Integrity, Repair and Replication
url 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
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