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

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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. J. Cell. Biochem. 100: 385–401, 2007.