Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway
Citations Over TimeTop 1% of 2015 papers
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.
Related Papers
- → Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends(2007)166 cited
- Deficient nonhomologous end-joining activity in cell-free extracts from Brca1-null fibroblasts.(2002)
- → Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks(2008)74 cited
- → Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytes(2016)53 cited
- → Double-Strand Breaks Repair by Non-Homologous DNA End Joining in Mammalian Cells(2006)1 cited