Rulten, Stuart L., Fisher, Anna E O, Robert, Isabelle, Zuma, Maria C., Rouleau, Michele, Ju, Limei, Poirier, Guy, Reina-San-Martin, Bernardo and Caldecott, Keith W. (2010) PARP-3 and APLF Function Together to Accelerate Non-Homologous End Joining. Molecular Cell, 41 (1). pp. 33-45. ISSN 1097-2765

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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.

Item Type:	Article
Additional Information:	GDSC339
Keywords:	DNA repair; poly (ADP-ribose) polymerase; non homologous end joining; APLF; double strand break
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects:	Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Depositing User:	Gee Wheatley
Date Deposited:	26 Nov 2010
Last Modified:	07 Mar 2017 08:12
URI:	http://sro.sussex.ac.uk/id/eprint/2555
Google Scholar:	18 Citations

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