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

Rulten, Stuart L, Fisher, Anna E O, Robert, Isabelle, Zuma, Maria C, Rouleau, Michele, Ju, Limei, Poirer, Guy, Reina-San-Martin, Bernardo and Caldecott, Keith W (2011) PARP-3 and APLF function together to accelerate nonhomologous end-joining. Molecular Cell, 41 (1). pp. 33-45. ISSN 1097-2765

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Stuart Rulten
Date Deposited: 06 Feb 2012 19:49
Last Modified: 09 Jul 2013 13:38
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