In vitro replication and repair studies of tandem lesions containing neighboring thymidine glycol and 8-oxo-7,8-dihydro-2'-deoxyguanosine.

Abstract:

:Reactive oxygen species can induce the formation of tandem DNA lesions. We recently showed that the treatment of calf thymus DNA with Cu2+/H2O2/ascorbate could result in the efficient formation of a tandem lesion where a 5,6-dihydroxy-5,6-dihydrothymidine (or thymidine glycol) is situated on the 5' side of an 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). In the present study, we assessed how the 5'-Tg-(8-oxodG)-3' and 5'-(8-oxodG)-Tg-3' tandem lesions are replicated by purified DNA polymerases and how they are recognized by base excision repair enzymes. Our results revealed that the tandem lesions blocked primer extension mediated by the Klenow fragment and yeast polymerase eta more readily than when the Tg or 8-oxodG was present alone. The mutagenic properties of Tg or 8-oxodG differed while they were present alone or in tandem. Moreover, the human 8-oxoguanine-DNA glycosylase (hOGG1)-mediated cleavage of 8-oxodG was compromised considerably by the presence of a neighboring 5' Tg, whereas the presence of Tg as the adjacent 3' nucleoside enhanced 8-oxodG cleavage by hOGG1. The efficiency for the cleavage of Tg by endonuclease III was not affected by the presence of an adjoining 8-oxodG. These results supported the notion that the replication and repair of tandem single-nucleobase lesions depend on the types of lesions involved and their spatial arrangement.

journal_name

Chem Res Toxicol

authors

Jiang Y,Wang Y,Wang Y

doi

10.1021/tx8003449

subject

Has Abstract

pub_date

2009-03-16 00:00:00

pages

574-83

issue

3

eissn

0893-228X

issn

1520-5010

pii

10.1021/tx8003449

journal_volume

22

pub_type

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