Parp-1 deficiency causes an increase of deletion mutations and insertions/rearrangements in vivo after treatment with an alkylating agent
Open Access
- 20 December 2004
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 24 (8) , 1328-1337
- https://doi.org/10.1038/sj.onc.1208289
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 (PParp-1−/− than in Parp-1+/+ mice (Pgpt 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.Keywords
This publication has 58 references indexed in Scilit:
- Efficient method for mapping and characterizing structures of deletion mutations ingpt delta mice using Southern blot analysis with oligo DNA probesEnvironmental and Molecular Mutagenesis, 2004
- Mechanism and regulation of human non-homologous DNA end-joiningNature Reviews Molecular Cell Biology, 2003
- Improvement of the Spi- assay for mutations ingpt delta mice by including magnesium ions during plaque formationEnvironmental and Molecular Mutagenesis, 2003
- Efficient detection of deletions induced by a single treatment of mitomycin C in transgenic mousegpt delta using the Spi? selectionEnvironmental and Molecular Mutagenesis, 1999
- Spectra ofgpt mutations in ethylnitrosourea-treated and untreated transgenic miceEnvironmental and Molecular Mutagenesis, 1999
- In vitro repair of synthetic ionizing radiation-induced multiply damaged DNA sites 1 1Edited by J. H. MillerJournal of Molecular Biology, 1999
- Genetic interaction between PARP and DNA-PK in V(D)J recombination and tumorigenesisNature Genetics, 1997
- ADP-Ribosylation of Wild-Type p53in Vitro:Binding of p53 Protein to Specific p53 Consensus Sequence Prevents Its ModificationBiochemical and Biophysical Research Communications, 1996
- Inhibitors of poly(adenosine diphosphate ribose) polymerase induce sister chromatid exchangesBiochemical and Biophysical Research Communications, 1980
- Enzyme-bound early product of purified poly(ADP-ribose) polymeraseBiochemical and Biophysical Research Communications, 1977