PARP-2 Another Actor in Base Excision Repair

PARP-2 Another Actor in Base Excision Repair 

To examine the contribudon of PARP-1 and PARP-2 on the recruitment of XRCCl, wt, PARP-T and PARP-2 3T3 cells were microirradiaied. While no recruitment ofXRjCCl could be detected in most of the PARP-l cells (Fig. lOB, d-f), an efficient recruitment of XRCCl comparable to wt cells was still observed in PARP-2 cells (Rg. lOB, g-h). This result demonstrates that poiy(ADP-ribose) synthedxed by PARP-1 immediacy tri ers the rapid accumuladon of XRCCl at DNA breaks. Furthermore, this residt strengthens the idea that PARP-2 is not involved in the DNA damage rect nition step of SSBR/BER pathway, but in a subsequent step of the repair process, leadii when absent, to a repair defect as observed by the COMET assay. 

What could be the step at which PARP-2 is required for efficient SSBR/BEIV Identifying what is the DNA target of PARP-2, likely diHerent to that of PARP-1 due to their distinct DNA binding domains is of pardcular interest to answer this question. 

The presence of PARP-2 in r ions of the genome containing repetitive DNA sequences like centromeres, telomeres and rONA and in association with X-chtomosome surest a role of PARP-2 in the maintenance of both constitutive and facultative heterochromatin integrity, which may become a target for pharmacological intervention. 

We thank Dr. Sugimura for the lOH anti-poly(ADP-ribose) antibody. We are gratefiil to Oidier Hentsch (IGBMC, lUkirch) and Jean-Christophe Laval (Leica Microsystems, France) for their help with the laser microbeam. This work was supported by funds from Centre Nadonal de la Recherche Scientifique, Association pour la Recherche Contre le Cancer, Electricity de France, Ligue Nationale Contre le Cancer and Commissariat k I Energie Atomique. 

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