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Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks

Repair of DNA double-strand breaks (DSBs) requires eviction of the histones around DNA breaks to allow the loading of numerous repair and checkpoint proteins. However, the mechanism and regulation of this process remain poorly understood. Here, we show that histone H2B ubiquitination (uH2B) promotes...

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Autores principales: Zheng, Sihao, Li, Dan, Lu, Zhen, Liu, Guangxue, Wang, Meng, Xing, Poyuan, Wang, Min, Dong, Yang, Wang, Xuejie, Li, Jingyao, Zhang, Simin, Peng, Haoyang, Ira, Grzegorz, Li, Guohong, Chen, Xuefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265479/
https://www.ncbi.nlm.nih.gov/pubmed/30304473
http://dx.doi.org/10.1093/nar/gky918
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author Zheng, Sihao
Li, Dan
Lu, Zhen
Liu, Guangxue
Wang, Meng
Xing, Poyuan
Wang, Min
Dong, Yang
Wang, Xuejie
Li, Jingyao
Zhang, Simin
Peng, Haoyang
Ira, Grzegorz
Li, Guohong
Chen, Xuefeng
author_facet Zheng, Sihao
Li, Dan
Lu, Zhen
Liu, Guangxue
Wang, Meng
Xing, Poyuan
Wang, Min
Dong, Yang
Wang, Xuejie
Li, Jingyao
Zhang, Simin
Peng, Haoyang
Ira, Grzegorz
Li, Guohong
Chen, Xuefeng
author_sort Zheng, Sihao
collection PubMed
description Repair of DNA double-strand breaks (DSBs) requires eviction of the histones around DNA breaks to allow the loading of numerous repair and checkpoint proteins. However, the mechanism and regulation of this process remain poorly understood. Here, we show that histone H2B ubiquitination (uH2B) promotes histone eviction at DSBs independent of resection or ATP-dependent chromatin remodelers. Cells lacking uH2B or its E3 ubiquitin ligase Bre1 exhibit hyper-resection due to the loss of H3K79 methylation that recruits Rad9, a known negative regulator of resection. Unexpectedly, despite excessive single-strand DNA being produced, bre1Δ cells show defective RPA and Rad51 recruitment and impaired repair by homologous recombination and response to DNA damage. The HR defect in bre1Δ cells correlates with impaired histone loss at DSBs and can be largely rescued by depletion of CAF-1, a histone chaperone depositing histones H3-H4. Overexpression of Rad51 stimulates histone eviction and partially suppresses the recombination defects of bre1Δ mutant. Thus, we propose that Bre1 mediated-uH2B promotes DSB repair through facilitating histone eviction and subsequent loading of repair proteins.
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spelling pubmed-62654792018-12-04 Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks Zheng, Sihao Li, Dan Lu, Zhen Liu, Guangxue Wang, Meng Xing, Poyuan Wang, Min Dong, Yang Wang, Xuejie Li, Jingyao Zhang, Simin Peng, Haoyang Ira, Grzegorz Li, Guohong Chen, Xuefeng Nucleic Acids Res Genome Integrity, Repair and Replication Repair of DNA double-strand breaks (DSBs) requires eviction of the histones around DNA breaks to allow the loading of numerous repair and checkpoint proteins. However, the mechanism and regulation of this process remain poorly understood. Here, we show that histone H2B ubiquitination (uH2B) promotes histone eviction at DSBs independent of resection or ATP-dependent chromatin remodelers. Cells lacking uH2B or its E3 ubiquitin ligase Bre1 exhibit hyper-resection due to the loss of H3K79 methylation that recruits Rad9, a known negative regulator of resection. Unexpectedly, despite excessive single-strand DNA being produced, bre1Δ cells show defective RPA and Rad51 recruitment and impaired repair by homologous recombination and response to DNA damage. The HR defect in bre1Δ cells correlates with impaired histone loss at DSBs and can be largely rescued by depletion of CAF-1, a histone chaperone depositing histones H3-H4. Overexpression of Rad51 stimulates histone eviction and partially suppresses the recombination defects of bre1Δ mutant. Thus, we propose that Bre1 mediated-uH2B promotes DSB repair through facilitating histone eviction and subsequent loading of repair proteins. Oxford University Press 2018-11-30 2018-10-10 /pmc/articles/PMC6265479/ /pubmed/30304473 http://dx.doi.org/10.1093/nar/gky918 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genome Integrity, Repair and Replication
Zheng, Sihao
Li, Dan
Lu, Zhen
Liu, Guangxue
Wang, Meng
Xing, Poyuan
Wang, Min
Dong, Yang
Wang, Xuejie
Li, Jingyao
Zhang, Simin
Peng, Haoyang
Ira, Grzegorz
Li, Guohong
Chen, Xuefeng
Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks
title Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks
title_full Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks
title_fullStr Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks
title_full_unstemmed Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks
title_short Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks
title_sort bre1-dependent h2b ubiquitination promotes homologous recombination by stimulating histone eviction at dna breaks
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265479/
https://www.ncbi.nlm.nih.gov/pubmed/30304473
http://dx.doi.org/10.1093/nar/gky918
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