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 (2011) PARP-3 and APLF function together to accelerate nonhomologous end joining. Molecular Cell, 41 (1). pp. 33-45. ISSN 1097-2765
![]() |
PDF
- Accepted Version
Download (1MB) |
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: | 29 Nov 2017 17:04 |
URI: | http://sro.sussex.ac.uk/id/eprint/2555 |
Google Scholar: | 18 Citations |
View download statistics for this item
📧 Request an update