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Nucleic Acids Symposium Series 2007 51(1):49-50; doi:10.1093/nass/nrm025
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© 2007 Oxford University Press

Nucleotide incorporation against 7,8-dihydro-8-oxoguanine is influenced by neighboring base sequences in TLS DNA polymerase reaction

ChinWei Yung1,*, Tetsuya Suzuki2, Yoji Okugawa2, Asako Kawakami2, David Loakes3, Kazuo Negishi1 and Tomoe Negishi4

1Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
2Department of Genomic and Proteomics, Okayama University Advanced Science Research Center, Tsushima, Okayama, Japan.
3Medical Research Council, Laboratory of Molecular Biology, Hill Road, Cambridge CB2 2QH UK.
4Nihon Pharmaceutical University, Japan.

*Email: isaka{at}pharm.okayama-u.ac.jp

Abstract

7,8-Dihydro-8-oxoguanine (8-oxoG) is a well-known oxidative lesion in DNA and is related to carcinogenesis and ageing processes. Misincorporation of dATP opposite to 8-oxoG leads to G -> T transversion mutations. DNA sequence has been proved as an important factor influencing the replication and enzymatic repair of various types of damages. To explore the influence of sequence effect on the properties of translesion synthesis (TLS) polymerase bypass of 8-oxoG, oligonucleotides with an 8-oxoG in different sequence contexts were used. We conclude that the 5'-nearest base next to 8-oxoG has significant effects in the G -> T mutation by hpol{eta}.


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