Ochi T., Blackford AN., Coates J., Jhujh S., Mehmood S., Tamura N., Travers J., Wu Q., Draviam VM., Robinson CV., Blundell TL., Jackson SP.

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.

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

Ochi T., Blackford AN., Coates J., Jhujh S., Mehmood S., Tamura N., Travers J., Wu Q., Draviam VM., Robinson CV., Blundell TL., Jackson SP.

DOI

Type

Journal

Publication Date

Volume

Pages

Keywords