Interactome Analysis Identifies a New Paralogue of XRCC4 in Non-homologous End Joining DNA Repair Pathway

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Feb 12

PMID 25670504

Citations 105

Authors

Mengtan Xing

Mingrui Yang

Wei Huo

Feng Feng

Leizhen Wei

Wenxia Jiang

Shaokai Ning

Zhenxin Yan

Wen Li

Qingsong Wang

Mei Hou

Chunxia Dong

Rong Guo

Ge Gao

Jianguo Ji

Shan Zha

Li Lan

Huanhuan Liang

Dongyi Xu

Affiliations

Soon will be listed here.

Abstract

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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