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Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway
Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it is unclear how NHEJ factors organize to repair diverse types of DNA breaks. Here, through systematic analysis of the human NHEJ factor interac...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339890/ https://www.ncbi.nlm.nih.gov/pubmed/25670504 http://dx.doi.org/10.1038/ncomms7233 |
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author | Xing, Mengtan Yang, Mingrui Huo, Wei Feng, Feng Wei, Leizhen Jiang, Wenxia Ning, Shaokai Yan, Zhenxin Li, Wen Wang, Qingsong Hou, Mei Dong, Chunxia Guo, Rong Gao, Ge Ji, Jianguo Zha, Shan Lan, Li Liang, Huanhuan Xu, Dongyi |
author_facet | Xing, Mengtan Yang, Mingrui Huo, Wei Feng, Feng Wei, Leizhen Jiang, Wenxia Ning, Shaokai Yan, Zhenxin Li, Wen Wang, Qingsong Hou, Mei Dong, Chunxia Guo, Rong Gao, Ge Ji, Jianguo Zha, Shan Lan, Li Liang, Huanhuan Xu, Dongyi |
author_sort | Xing, Mengtan |
collection | PubMed |
description | Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it is unclear how NHEJ factors organize to repair diverse types of DNA breaks. Here, through systematic analysis of the human NHEJ factor interactome, we identify PAXX as a direct interactor of Ku. The crystal structure of PAXX is similar to those of XRCC4 and XLF. Importantly, PAXX-deficient cells are sensitive to DSB-causing agents. Moreover, epistasis analysis demonstrates that PAXX functions together with XLF in response to ionizing radiation-induced complex DSBs, whereas they function redundantly in response to Topo2 inhibitor-induced simple DSBs. Consistently, PAXX and XLF coordinately promote the ligation of complex but not simple DNA ends in vitro. Altogether, our data identify PAXX as a new NHEJ factor and provide insight regarding the organization of NHEJ factors responding to diverse types of DSB ends. |
format | Online Article Text |
id | pubmed-4339890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43398902015-03-02 Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway Xing, Mengtan Yang, Mingrui Huo, Wei Feng, Feng Wei, Leizhen Jiang, Wenxia Ning, Shaokai Yan, Zhenxin Li, Wen Wang, Qingsong Hou, Mei Dong, Chunxia Guo, Rong Gao, Ge Ji, Jianguo Zha, Shan Lan, Li Liang, Huanhuan Xu, Dongyi Nat Commun Article Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it is unclear how NHEJ factors organize to repair diverse types of DNA breaks. Here, through systematic analysis of the human NHEJ factor interactome, we identify PAXX as a direct interactor of Ku. The crystal structure of PAXX is similar to those of XRCC4 and XLF. Importantly, PAXX-deficient cells are sensitive to DSB-causing agents. Moreover, epistasis analysis demonstrates that PAXX functions together with XLF in response to ionizing radiation-induced complex DSBs, whereas they function redundantly in response to Topo2 inhibitor-induced simple DSBs. Consistently, PAXX and XLF coordinately promote the ligation of complex but not simple DNA ends in vitro. Altogether, our data identify PAXX as a new NHEJ factor and provide insight regarding the organization of NHEJ factors responding to diverse types of DSB ends. Nature Pub. Group 2015-02-11 /pmc/articles/PMC4339890/ /pubmed/25670504 http://dx.doi.org/10.1038/ncomms7233 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Xing, Mengtan Yang, Mingrui Huo, Wei Feng, Feng Wei, Leizhen Jiang, Wenxia Ning, Shaokai Yan, Zhenxin Li, Wen Wang, Qingsong Hou, Mei Dong, Chunxia Guo, Rong Gao, Ge Ji, Jianguo Zha, Shan Lan, Li Liang, Huanhuan Xu, Dongyi Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway |
title | Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway |
title_full | Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway |
title_fullStr | Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway |
title_full_unstemmed | Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway |
title_short | Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway |
title_sort | interactome analysis identifies a new paralogue of xrcc4 in non-homologous end joining dna repair pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339890/ https://www.ncbi.nlm.nih.gov/pubmed/25670504 http://dx.doi.org/10.1038/ncomms7233 |
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