PARP-3 associates with polycomb group bodies and with components of the DNA damage repair machinery.

Abstract

Poly(ADP-ribose) polymerase 3 (PARP-3) is a novel member of the PARP family of enzymes that synthesize poly(ADP-ribose) on themselves and other acceptor proteins. Very little is known about this PARP, which is closely related to PARP-1 and PARP-2. By sequence analysis, we find that PARP-3 may be expressed in two isoforms which we studied in more detail to gain insight into their possible functions. We find that both PARP-3 isoforms, transiently expressed as GFP or FLAG fusions, are nuclear. Detection of endogenous PARP-3 with a specific antibody also shows a widespread nuclear distribution, appearing in numerous small foci and a small number of larger foci. Through co-localization experiments and immunoprecipitations, the larger nuclear foci were identified as Polycomb group bodies (PcG bodies) and we found that PARP-3 is part of Polycomb group protein complexes. Furthermore, using a proteomics approach, we determined that both PARP-3 isoforms are part of complexes comprising DNA-PKcs, PARP-1, DNA ligase III, DNA ligase IV, Ku70, and Ku80. Our findings suggest that PARP-3 is a nuclear protein involved in transcriptional silencing and in the cellular response to DNA damage.

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@article{Rouleau2007PARP3AW, title={PARP-3 associates with polycomb group bodies and with components of the DNA damage repair machinery.}, author={Mich{\`e}le Rouleau and D A Mcdonald and Paul J. Gagne and M Ouellet and Arnaud Droit and Jennifer M. Hunter and St{\'e}phanie Dutertre and Catherine Prigent and Michael J. Hendzel and Guy G. Poirier}, journal={Journal of cellular biochemistry}, year={2007}, volume={100 2}, pages={385-401} }