Suppression of γ-irradiation-induced deletion mutations under Parp-1 deficiency in mice
Journal Title: Scholars Academic Journal of Biosciences - Year 2015, Vol 3, Issue 12
Abstract
Abstract: Poly (ADP-ribose) polymerase-1 (Parp-1) functions in DNA repair, acting as a sensor for DNA strand breaks and recruiting DNA repair proteins to the site of DNA damage. To investigate the impact of Parp-1 in processing of DNA damages and genomic stability after γ-irradiation, we performed in vivo mutation analysis utilizing gpt delta transgenic mice in the liver and brain under Parp-1 deficiency. The mutant frequencies increased 3-fold in Parp-1+/+ mice in the liver 3 days after γ-irradiation at 8 Gy, whereas those of Parp-1 knockout (Parp-1-/-) mice did not increase. When the mutation spectra in the livers were analyzed, the frequencies of simple-type deletion mutations were lower in the Parp-1-/- mice. Notably, one base deletion mutations at hot-spots of 4-6 mononucleotide repeats were 4-fold lower in the Parp-1-/- liver (P<0.05). In the brain, the mutant frequencies did not increase in both genotypes after γ-irradiation. These results suggest that PARP-1 is required in the induction of γ-irradiation-induced deletion mutations in the liver possibly through supporting inaccurate DNA repair processes. Keywords: γ-irradiation, PARP-1, deletion mutation, liver, brain.
Authors and Affiliations
Junhui Wang, Masahiro Abe, Erika Sasamoto, Daisuke Maeda, Yoshikazu Sugimoto, shio Miki, Mitsuko Masutani
Keywords
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