PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice.

ABSTRACT: Non-homologous end-joining (NHEJ) is the most prominent DNA double strand break (DSB) repair pathway in mammalian cells. PAXX is the newest NHEJ factor, which shares structural similarity with known NHEJ factors-XRCC4 and XLF. Here we report that PAXX is dispensable for physiological NHEJ in otherwise wild-type mice. Yet Paxx^-/- mice require XLF and Xlf^-/- mice require PAXX for end-ligation. As such, Xlf^-/-Paxx^-/- mice display severe genomic instability and neuronal apoptosis, which eventually lead to embryonic lethality. Despite their structural similarities, only Xlf^-/- cells, but not Paxx^-/- cells require ATM/DNA-PK kinase activity for end-ligation. Mechanistically, PAXX promotes the accumulation of KU at DSBs, while XLF

SUBMITTER: Liu X 

PROVIDER: S-EPMC5216128 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature