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Mol Biol (Mosk). 2007 Jan-Feb;41(1):112-20.

[Interactions of pro- and eukaryotic DNA repair enzymes with oligodeoxyribonucleotides containing clustered lesions].

[Article in Russian]

Abstract

Interactions of oxoGuanine-DNA glycosylases from Escherichia coli (Fpg) and human (OGG1) and abasic site endonucleases from yeast (Apnl) and E. coli (Nfo) with oligodeoxyribonucleotides containing oxoGuanine (oxoG) and tetrahydrofuran (F, a stable analog of an abasic site) separated by various numbers of nucleotides have been studied. Inhibitor analysis has shown that the affinity of Fpg for single-stranded ligands does not depend on the relative positions of oxoG and F lesions. KM and kcat values have been determined for all double-stranded substrates and all enzymes under study. The effect of introducing the second lesion was strongly dependent on the relative positions of the lesions and the nature of the enzyme. The highest drop in the affinity (1.6-148-fold) and the reaction rate (4.8-58-fold) has been observed with Fpg and OGG1 for substrates containing F immediately 5' or 3' adjacent to oxoG. Introduction of the second lesion barely changed the KM values for Apnl and Nfo substrates. At the same time, the reaction rates were 5-10-fold lower for substrates containing two adjacent lesions. For all enzymes studied, increasing the distance between two lesions in duplex DNA reduced the effect of the lesion in KM and kcat values.

PMID:
17380898
[Indexed for MEDLINE]

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