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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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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. |
format | Online Article Text |
id | pubmed-9508856 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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