| First Author | Louro H | Year | 2008 |
| Journal | Mutat Res | Volume | 640 |
| Issue | 1-2 | Pages | 82-8 |
| PubMed ID | 18242645 | Mgi Jnum | J:133514 |
| Mgi Id | MGI:3778729 | Doi | 10.1016/j.mrfmmm.2007.12.003 |
| Citation | Louro H, et al. (2008) Mutagenic effects of poly (ADP-ribose) polymerase-1 deficiency in transgenic mice. Mutat Res 640(1-2):82-8 |
| abstractText | Poly (ADP-ribose) polymerase-1 (Parp1) plays a central role in the maintenance of genomic integrity and has been unequivocally associated to DNA base excision repair (BER) but its involvement in double-strand break (DSB) repair pathways remains unclear. In this work, using transgenic Parp1-deficient mice harbouring the lacZ reporter gene, we provide in vivo evidence that Parp1 contributes to the prevention of deletions/insertions in testis following an alkylation insult. In response to N-Methyl-N-Nitrosurea (MNU) treatment no significant difference in the mutant frequency (MF) in the liver and testis could be attributed to Parp1 status, given that both Parp1(+/+) and Parp1(-/-) mice showed a similar significant increase in the overall MF. However, restriction analysis of MNU-induced mutants evidenced a shift in the distribution of mutations between deletions/insertions and point mutations in testis, but not in the liver, dependent on the Parp1 status. A significant higher frequency of deletions/insertions was observed in testis from Parp1(-/-) in comparison to Parp1(+/+) mice, whereas point mutations were not significantly affected. Overall, our findings show that Parp1 participates in the prevention of deletions/insertions induced by methylating agents and that organ-specific factors may influence its capacity to protect against genotoxic damage. |
