Number : MOLECULAR - CELL - D - 10 - 00462 R 3 Title : PARP - 3 and APLF Function Together to Accelerate Non - Homologous End Joining
نویسندگان
چکیده
PARP-3 is a member of the ADP-ribosyl transferase super-family of unknown function. We show that PARP-3 is stimulated by DNA double-strand breaks (DSBs) in vitro and functions in the same pathway as the poly (ADP-ribose)-binding protein APLF to accelerate chromosomal DNA doublestrand break repair. We implicate PARP-3 in the accumulation of APLF at DSBs and demonstrate that APLF promotes the retention of XRCC4/DNA ligase IV complex in chromatin, suggesting that PARP-3 and APLF accelerate DNA ligation during non-homologous end-joining (NHEJ). Consistent with this, we show that class-switch recombination in Aplf-/B cells is biased towards microhomology-mediated end-joining, a pathway that operates in the absence of XRCC4/DNA ligase IV, and that the requirement for PARP-3 and APLF for NHEJ is circumvented by overexpression of XRCC4/DNA ligase IV. These data identify molecular roles for PARP-3 and APLF and uncover a novel and unanticipated aspect of chromosomal DNA double-strand break repair reactions. Suggested Reviewers:
منابع مشابه
PARP-3 and APLF function together to accelerate nonhomologous end-joining.
PARP-3 is a member of the ADP-ribosyl transferase superfamily of unknown function. We show that PARP-3 is stimulated by DNA double-strand breaks (DSBs) in vitro and functions in the same pathway as the poly (ADP-ribose)-binding protein APLF to accelerate chromosomal DNA DSB repair. We implicate PARP-3 in the accumulation of APLF at DSBs and demonstrate that APLF promotes the retention of XRCC4/...
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