PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair

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 direc...

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Published in:Science (American Association for the Advancement of Science) 2015-01, Vol.347 (6218), p.185-188
Main Authors: Ochi, Takashi, Blackford, Andrew N., Coates, Julia, Jhujh, Satpal, Mehmood, Shahid, Tamura, Naoka, Travers, Jon, Wu, Qian, Draviam, Viji M., Robinson, Carol V., Blundell, Tom L., Jackson, Stephen P.
Format: Article
Language:English
Subjects:
Breaking
Deoxyribonucleic acid
DNA repair
Genomics
In vitro testing
Maintenance
Proteins
Repair
Ribonucleic acids
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1261971