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- Title
Parp-1 deficiency causes an increase of deletion mutations and insertions/rearrangements in vivo after treatment with an alkylating agent.
- Authors
Shibata, Atsushi; Kamada, Nobuo; Masumura, Ken-ichi; Nohmi, Takehiko; Kobayashi, Shizuko; Teraoka, Hirobumi; Nakagama, Hitoshi; Sugimura, Takashi; Suzuki, Hiroshi; Masutani, Mitsuko
- Abstract
Accumulated evidence suggests that Parp-1 is involved in DNA repair processes, including base excision repair, single-strand and double-strand break repairs. To understand the precise role of Parp-1 in genomic stability in vivo, we carried out mutation analysis using Parp-1 knockout (Parp-1-/-) mice harboring two marker genes, gpt and red/gam genes. Spontaneous mutant frequencies of both genes in the bone marrows and livers did not differ significantly between Parp-1-/- and Parp-1+/+ mice (P>0.05). After treatment with an alkylating agent, N-nitrosobis(2-hydroxypropyl)amine (BHP), the mutant frequency of the red/gam genes in the liver in Parp-1-/- mice was 1.6-fold higher than that in Parp-1+/+ mice (P<0.05). Categorization of the mutations revealed that deletions larger than 1?kb or those accompanying 1-5?bp insertions at the deletion junctions, as well as rearrangements, were more frequently observed in Parp-1-/- than in Parp-1+/+ mice (P<0.05, respectively). In contrast, mutant frequencies of the gpt gene in the livers of Parp-1-/- and Parp-1+/+ mice after BHP treatment were both elevated and there was no significant difference between the genotypes. These results indicate that Parp-1 is implicated in suppressing deletion mutations in vivo, especially those accompanying small insertions or rearrangements.Oncogene (2005) 24, 1328-1337. doi:10.1038/sj.onc.1208289 Published online 20 December 2004
- Subjects
DNA repair; BIOCHEMICAL genetics; GENOMICS; GENETIC mutation; GENETICS; GENES
- Publication
Oncogene, 2005, Vol 24, Issue 8, p1328
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208289