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-CGG o, each possessing a single 8-oxoG residue and represented by the sequences 5′-CCGo-3′ and 5′-CGGo- 3′, 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 5′-CCGo-3′ 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 5′-CCGo-3′ 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 5′-CCG o-3′ sequence. © The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.
CITATION STYLE
Yung, C. W., Okugawa, Y., Otsuka, C., Okamoto, K., Arimoto, S., Loakes, D., … Negishi, T. (2008). Influence of neighbouring base sequences on the mutagenesis induced by 7,8-dihydro-8-oxoguanine in yeast. Mutagenesis, 23(6), 509–513. https://doi.org/10.1093/mutage/gen044
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