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Ionizing radiation induces clustered DNA damage where two or more lesions are located proximal to each other on the same or opposite DNA strands. It has been suggested that individual lesions within a cluster are removed sequentially and that the presence of a vicinal lesion(s) may affect the rate and fidelity of DNA repair. In this study, we addressed the question of how 8-oxoguanine located opposite to normal or reduced abasic sites would affect the repair of these sites by the base excision repair system. We have found that an 8-oxoguanine located opposite to an abasic site does not affect either the efficiency or fidelity of repair synthesis by DNA polymerase beta. In contrast, an 8-oxoguanine located one nucleotide 3'-downstream of the abasic site significantly reduces both strand displacement synthesis supported by DNA polymerase beta or delta and cleavage by flap endonuclease of the generated flap, thus inhibiting the long-patch base excision repair pathway.

Original publication

DOI

10.1074/jbc.M201918200

Type

Journal article

Journal

J Biol Chem

Publication Date

14/06/2002

Volume

277

Pages

21300 - 21305

Keywords

DNA Damage, DNA Polymerase beta, DNA Repair, DNA-Directed DNA Polymerase, Dose-Response Relationship, Drug, Guanine, Humans, Recombinant Proteins, Time Factors