Parp-1 deficiency causes an increase of deletion mutations and insertions/rearrangements in vivo after treatment with an alkylating agent

Atsushi Shibata, Nobuo Kamada, Ken Ichi Masumura, Takehiko Nohmi, Shizuko Kobayashi, Hirobumi Teraoka, Hitoshi Nakagama, Takashi Sugimura, Hiroshi Suzuki, Mitsuko Masutani

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

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 fed/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.

Original languageEnglish
Pages (from-to)1328-1337
Number of pages10
JournalOncogene
Volume24
Issue number8
DOIs
Publication statusPublished - 2005 Feb 17

Keywords

  • Deletion
  • gpt delta
  • Mutation
  • Parp-1
  • Rearrangement
  • Recombination

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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