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/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. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Stuart L Rulten, Anna E O Fisher, Isabelle Robert, Maria C Zuma, Michele Rouleau, Limei Ju, Guy Poirier, Bernardo Reina-San-Martin, Keith W Caldecott. PARP-3 and APLF function together to accelerate nonhomologous end-joining. Molecular cell. 2011 Jan 07;41(1):33-45

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PMID: 21211721

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