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MRNIP condensates promote DNA double-strand break sensing and end resection
The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-med...
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/PMC9098523/ https://www.ncbi.nlm.nih.gov/pubmed/35551189 http://dx.doi.org/10.1038/s41467-022-30303-w |
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author | Wang, Yun-Long Zhao, Wan-Wen Bai, Shao-Mei Feng, Li-Li Bie, Shu-Ying Gong, Li Wang, Fang Wei, Ming-Biao Feng, Wei-Xing Pang, Xiao-Lin Qin, Cao-Litao Yin, Xin-Ke Wang, Ying-Nai Zhou, Weihua Wahl, Daniel R. Liu, Quentin Chen, Ming Hung, Mien-Chie Wan, Xiang-Bo |
author_facet | Wang, Yun-Long Zhao, Wan-Wen Bai, Shao-Mei Feng, Li-Li Bie, Shu-Ying Gong, Li Wang, Fang Wei, Ming-Biao Feng, Wei-Xing Pang, Xiao-Lin Qin, Cao-Litao Yin, Xin-Ke Wang, Ying-Nai Zhou, Weihua Wahl, Daniel R. Liu, Quentin Chen, Ming Hung, Mien-Chie Wan, Xiang-Bo |
author_sort | Wang, Yun-Long |
collection | PubMed |
description | The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection. |
format | Online Article Text |
id | pubmed-9098523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90985232022-05-14 MRNIP condensates promote DNA double-strand break sensing and end resection Wang, Yun-Long Zhao, Wan-Wen Bai, Shao-Mei Feng, Li-Li Bie, Shu-Ying Gong, Li Wang, Fang Wei, Ming-Biao Feng, Wei-Xing Pang, Xiao-Lin Qin, Cao-Litao Yin, Xin-Ke Wang, Ying-Nai Zhou, Weihua Wahl, Daniel R. Liu, Quentin Chen, Ming Hung, Mien-Chie Wan, Xiang-Bo Nat Commun Article The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection. Nature Publishing Group UK 2022-05-12 /pmc/articles/PMC9098523/ /pubmed/35551189 http://dx.doi.org/10.1038/s41467-022-30303-w Text en © The Author(s) 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 Wang, Yun-Long Zhao, Wan-Wen Bai, Shao-Mei Feng, Li-Li Bie, Shu-Ying Gong, Li Wang, Fang Wei, Ming-Biao Feng, Wei-Xing Pang, Xiao-Lin Qin, Cao-Litao Yin, Xin-Ke Wang, Ying-Nai Zhou, Weihua Wahl, Daniel R. Liu, Quentin Chen, Ming Hung, Mien-Chie Wan, Xiang-Bo MRNIP condensates promote DNA double-strand break sensing and end resection |
title | MRNIP condensates promote DNA double-strand break sensing and end resection |
title_full | MRNIP condensates promote DNA double-strand break sensing and end resection |
title_fullStr | MRNIP condensates promote DNA double-strand break sensing and end resection |
title_full_unstemmed | MRNIP condensates promote DNA double-strand break sensing and end resection |
title_short | MRNIP condensates promote DNA double-strand break sensing and end resection |
title_sort | mrnip condensates promote dna double-strand break sensing and end resection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098523/ https://www.ncbi.nlm.nih.gov/pubmed/35551189 http://dx.doi.org/10.1038/s41467-022-30303-w |
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