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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
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.
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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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