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53BP1 regulates heterochromatin through liquid phase separation
Human 53BP1 is primarily known as a key player in regulating DNA double strand break (DSB) repair choice; however, its involvement in other biological process is less well understood. Here, we report a previously uncharacterized function of 53BP1 at heterochromatin, where it undergoes liquid-liquid...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766474/ https://www.ncbi.nlm.nih.gov/pubmed/35042897 http://dx.doi.org/10.1038/s41467-022-28019-y |
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author | Zhang, Lei Geng, Xinran Wang, Fangfang Tang, Jinshan Ichida, Yu Sharma, Arishya Jin, Sora Chen, Mingyue Tang, Mingliang Pozo, Franklin Mayca Wang, Wenxiu Wang, Janet Wozniak, Michal Guo, Xiaoxia Miyagi, Masaru Jin, Fulai Xu, Yongjie Yao, Xinsheng Zhang, Youwei |
author_facet | Zhang, Lei Geng, Xinran Wang, Fangfang Tang, Jinshan Ichida, Yu Sharma, Arishya Jin, Sora Chen, Mingyue Tang, Mingliang Pozo, Franklin Mayca Wang, Wenxiu Wang, Janet Wozniak, Michal Guo, Xiaoxia Miyagi, Masaru Jin, Fulai Xu, Yongjie Yao, Xinsheng Zhang, Youwei |
author_sort | Zhang, Lei |
collection | PubMed |
description | Human 53BP1 is primarily known as a key player in regulating DNA double strand break (DSB) repair choice; however, its involvement in other biological process is less well understood. Here, we report a previously uncharacterized function of 53BP1 at heterochromatin, where it undergoes liquid-liquid phase separation (LLPS) with the heterochromatin protein HP1α in a mutually dependent manner. Deletion of 53BP1 results in a reduction in heterochromatin centers and the de-repression of heterochromatic tandem repetitive DNA. We identify domains and residues of 53BP1 required for its LLPS, which overlap with, but are distinct from, those involved in DSB repair. Further, 53BP1 mutants deficient in DSB repair, but proficient in LLPS, rescue heterochromatin de-repression and protect cells from stress-induced DNA damage and senescence. Our study suggests that in addition to DSB repair modulation, 53BP1 contributes to the maintenance of heterochromatin integrity and genome stability through LLPS. |
format | Online Article Text |
id | pubmed-8766474 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87664742022-02-04 53BP1 regulates heterochromatin through liquid phase separation Zhang, Lei Geng, Xinran Wang, Fangfang Tang, Jinshan Ichida, Yu Sharma, Arishya Jin, Sora Chen, Mingyue Tang, Mingliang Pozo, Franklin Mayca Wang, Wenxiu Wang, Janet Wozniak, Michal Guo, Xiaoxia Miyagi, Masaru Jin, Fulai Xu, Yongjie Yao, Xinsheng Zhang, Youwei Nat Commun Article Human 53BP1 is primarily known as a key player in regulating DNA double strand break (DSB) repair choice; however, its involvement in other biological process is less well understood. Here, we report a previously uncharacterized function of 53BP1 at heterochromatin, where it undergoes liquid-liquid phase separation (LLPS) with the heterochromatin protein HP1α in a mutually dependent manner. Deletion of 53BP1 results in a reduction in heterochromatin centers and the de-repression of heterochromatic tandem repetitive DNA. We identify domains and residues of 53BP1 required for its LLPS, which overlap with, but are distinct from, those involved in DSB repair. Further, 53BP1 mutants deficient in DSB repair, but proficient in LLPS, rescue heterochromatin de-repression and protect cells from stress-induced DNA damage and senescence. Our study suggests that in addition to DSB repair modulation, 53BP1 contributes to the maintenance of heterochromatin integrity and genome stability through LLPS. Nature Publishing Group UK 2022-01-18 /pmc/articles/PMC8766474/ /pubmed/35042897 http://dx.doi.org/10.1038/s41467-022-28019-y Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Lei Geng, Xinran Wang, Fangfang Tang, Jinshan Ichida, Yu Sharma, Arishya Jin, Sora Chen, Mingyue Tang, Mingliang Pozo, Franklin Mayca Wang, Wenxiu Wang, Janet Wozniak, Michal Guo, Xiaoxia Miyagi, Masaru Jin, Fulai Xu, Yongjie Yao, Xinsheng Zhang, Youwei 53BP1 regulates heterochromatin through liquid phase separation |
title | 53BP1 regulates heterochromatin through liquid phase separation |
title_full | 53BP1 regulates heterochromatin through liquid phase separation |
title_fullStr | 53BP1 regulates heterochromatin through liquid phase separation |
title_full_unstemmed | 53BP1 regulates heterochromatin through liquid phase separation |
title_short | 53BP1 regulates heterochromatin through liquid phase separation |
title_sort | 53bp1 regulates heterochromatin through liquid phase separation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766474/ https://www.ncbi.nlm.nih.gov/pubmed/35042897 http://dx.doi.org/10.1038/s41467-022-28019-y |
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