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- Title
Influence of neighbouring base sequences on the mutagenesis induced by 7,8-dihydro-8-oxoguanine in yeast.
- Authors
Chin-Wei Yung; Yoji Okugawa; Chie Otsuka; Keinosuke Okamoto; Sakae Arimoto; David Loakes; Kazuo Negishi; Tomoe Negishi
- Abstract
We have analysed the influence of neighbouring base sequences on the mutagenesis induced by 7,8-dihydro-8-oxoguanine (8-oxoG or Go), a typical oxidative lesion of DNA, using the yeast oligonucleotide transformation technique. Two oligonucleotides, oligo-CCGo and oligo-CGGo, each possessing a single 8-oxoG residue and represented by the sequences 5â²-CCGo-3â² and 5â²-CGGo-3â², respectively, were introduced into a chromosome of Saccharomyces cerevisiae and their mutagenic potentials were compared. In a wild-type strain, 8-oxoG showed very weak mutagenic potential in both cases. However, the lesion in 5â²-CCGo-3â² can cause efficient G-to-T transversion in a strain lacking the rad30 gene which encodes yeast DNA polymerase η (Ypolη). To explore the properties associated with this translesion synthesis (TLS), the same two oligonucleotides possessing an 8-oxoG were used as templates for a standing-start primer extension assay, and the nucleotide incorporation opposite 8-oxoG was investigated. We found that dATP incorporation opposite 8-oxoG with Ypolη was low for both sequences. In particular, very low dATP incorporation was observed for the 5â²-CCGo-3â² sequence. These results account for the efficient inhibition of mutagenesis by Ypolη. TLS plays an important role in one DNA sequence in terms of avoiding mutagenesis induced by 8-oxoG in yeast. In contrast, human yeast DNA polymerase η showed higher dATP incorporation rates even with the 5â²-CCGo-3â² sequence.
- Subjects
MUTAGENESIS; DNA polymerases; NUCLEOTIDE sequence; OLIGONUCLEOTIDES; SACCHAROMYCES cerevisiae; MUTAGENS; CHROMOSOMES; ADENOSINE triphosphate
- Publication
Mutagenesis, 2008, Vol 23, Issue 6, p509
- ISSN
0267-8357
- Publication type
Article
- DOI
10.1093/mutage/gen044