| Autor: |
Kuipers, Gitta K, Slotman, Ben J, Poldervaart, Hester A, Reitsma-Wijker, Carola A, Lafleur, M.Vincent M |
| Zdroj: |
Mutation Research/DNA Repair; November 2000, Vol. 461 Issue: 3 p189-195, 7p |
| Abstrakt: |
One of the most predominating oxidative DNA damages, both spontaneously formed and after γ-radiation is 7,8-dihydro-8-oxoguanine (8oxoG). This 8oxoG is a mutagenic lesion because it can mispair with adenine instead of the correct cytosine leading to G:C to T:A transversions. In Escherichia coli(E. Coli) base excision repair (BER) is one of the most important repair systems for the repair of 8oxoG and other oxidative DNA damage. An important part of BER in E. coliis the so-called GO system which consists of three repair enzymes, MutM (Fpg), MutY and MutT which are all involved in repair of 8oxoG or 8oxoG mispairs. The aim of this study is to determine the effect of combined Fpg- and MutY-deficiency on the spontaneous and γ-radiation-induced mutation spectrum of the lacZαgene. For that purpose, non-irradiated or γ-irradiated double-stranded (ds) M13mp10 DNA, with the lacZαgene inserted as mutational target sequence was transfected into an E. colistrain which is deficient in both Fpg and MutY (BH1040). The resulting mutation spectra were compared with the mutation spectra of a fpg−E. colistrain (BH410) and a wild type E. colistrain (JM105) which were determined in an earlier study. The results of the present study indicate that combined Fpg- and MutY-deficiency induces a large increase in G:C to T:A transversions in both the spontaneous and γ-radiation-induced mutation spectra of BH1040 (fpg−mutY−) as compared to the fpg−and the wild type strain. Besides the increased levels of G:C to T:A transversions, there is also an increase in G:C to C:G transversions and frameshift mutations in both the spontaneous and γ-radiation-induced mutation spectra of BH1040 (fpg−mutY−). |
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