Inhibition of poly(ADP-ribose)polymerase stimulates extrachromosomal homologous recombination in mouse Ltk-fibroblasts

Abstract

Poly(ADP-ribose)polymerase (PARP) is an abundant nuclear enzyme activated by DNA breaks. PARP is generally believed to play a role in maintaining the integrity of the genome in eukaryote cells via antirecombinogenic activity by preventing inappropriate homologous recombination reactions at DNA double-strand breaks. While inhibition of PARP reduces non-homologous recombination, at the same time it stimulates sister chromatid exchange and intrachromosomal homologous recombination. Here we report that the inhibition of PARP with 100 μg/ml (0.622 mM) 1,5-isoquinolinediol results in an average 4.6-fold increase in the frequency of extrachromosomal homologous recombination between two linearized plasmids carrying herpes simplex virus thymidine kinase genes inactivated by non-overlapping mutations, in mouse Ltk- fibroblasts. These results are in disagreement with the previously reported observation that PARP inhibition had no effect on extrachromosomal homologous recombination in Ltk- cells.