Inhibition of poly(ADP-ribose)polymerase stimulates extrachromosomal homologous recombination in mouse Ltk-fibroblasts.
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 anti-recombinogenic 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 microg/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.
Semionov
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Departments of Oncology and Medicine, Faculty of Medicine, McGill University and Montreal General Hospital, 1650 Avenue Cedar, Montreal, Quebec H3G 1A4, Canada.
Cournoyer
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Chow
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D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D007546:Isoquinolines; D051379:Mice; D010957:Plasmids / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011804:Quinolines / Q000494:pharmacology; D011995:Recombination, Genetic / Q000187:drug effects
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011804:Quinolines; C095653:1,5-dihydroxyisoquinoline