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Mol Cell. 2011 Jan 7;41(1):33-45. doi: 10.1016/j.molcel.2010.12.006.

PARP-3 and APLF function together to accelerate nonhomologous end-joining.

Author information

1
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK.

Abstract

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/DNA ligase IV complex in chromatin, suggesting that PARP-3 and APLF accelerate DNA ligation during nonhomologous end-joining (NHEJ). Consistent with this, we show that class switch recombination in Aplf(-/-) B cells is biased toward 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 in chromosomal DNA double-strand break repair reactions.

PMID:
21211721
DOI:
10.1016/j.molcel.2010.12.006
[Indexed for MEDLINE]
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