Journal
MOLECULAR CELL
Volume 41, Issue 1, Pages 33-45Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2010.12.006
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Funding
- BBSRC [BB/F013930/1]
- MAC [G0600776]
- CR-UK [C6563/A101192]
- BBSRC [BB/F013930/1] Funding Source: UKRI
- MRC [G0600776] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F013930/1] Funding Source: researchfish
- Cancer Research UK [13078] Funding Source: researchfish
- Medical Research Council [G0600776, G0801130B] Funding Source: researchfish
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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.
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