title: DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair.
abstract: XRCC4 and XLF are two structurally related proteins that function in DNA double-strand break (DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and XLF, also called C9orf142) as a new XRCC4 superfamily member and show that its crystal structure resembles that of XRCC4. PAXX interacts directly with the DSB-repair protein Ku and is recruited to DNA-damage sites in cells. Using RNA interference and CRISPR-Cas9 to generate PAXX(-/-) cells, we demonstrate that PAXX functions with XRCC4 and XLF to mediate DSB repair and cell survival in response to DSB-inducing agents. Finally, we reveal that PAXX promotes Ku-dependent DNA ligation in vitro and assembly of core nonhomologous end-joining (NHEJ) factors on damaged chromatin in cells. These findings identify PAXX as a new component of the NHEJ machinery.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ochi
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Blackford
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Coates
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Satpal
authors.initials: S
authors.lastname: Jhujh
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Shahid
authors.initials: S
authors.lastname: Mehmood
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Naoka
authors.initials: N
authors.lastname: Tamura
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Travers
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Viji M
authors.initials: VM
authors.lastname: Draviam
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.|Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.|Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D017433:Protein Structure, Secondary; D034622:RNA Interference
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; C000595075:PAXX protein, human; C101467:XRCC4 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D045643:DNA Repair Enzymes