Mutagenic effects of poly (ADP-ribose) polymerase-1 deficiency in transgenic mice

Henriqueta Louro, Inês Pinheiro, Paula Costa, Carla Sousa, Anabela Dias, Maria G. Boavida, Maria J. Silva

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)82-88
Number of pages7
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume640
Issue number1-2
DOIs
Publication statusPublished - 2 Apr 2008

Keywords

  • Deletions
  • LacZ mice
  • MNU
  • Mutation pattern
  • Parp1

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