Substitution of 5-methylcytosines for cytosines enhances the stability of topoisomerase I-DNA complexes and modulates the sequence selectivity of camptothecin-induced DNA cleavage

We have investigated the binding and cleavage of DNA by human topoisomerase I using a 160 bp restriction fragment containing either natural bases or 5-methylcytosine residues in place of cytosines. Experiments were performed in the presence and absence of the antitumour drug camptothecin which speci...

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Veröffentlicht in:FEBS letters 1998-03, Vol.425 (2), p.337-340
Hauptverfasser: Carrasco, Carolina, Waring, Michael J, Bailly, Christian
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Bailly, Christian
description We have investigated the binding and cleavage of DNA by human topoisomerase I using a 160 bp restriction fragment containing either natural bases or 5-methylcytosine residues in place of cytosines. Experiments were performed in the presence and absence of the antitumour drug camptothecin which specifically inhibits topoisomerase I. Replacement of all cytosines with 5-methylcytosine residues (i) reinforces the enzyme-DNA interaction, (ii) enhances the stability of topoisomerase I-DNA complexes and (iii) modulates the sequence selectivity of camptothecin-induced DNA cleavage. The methyl group exposed in the major groove of the double helix is identified as a critical element for the interaction between topoisomerase I and DNA.
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subjects 5-Methylcytosine
Base Sequence
Camptothecin
Camptothecin - metabolism
Cytosine - analogs & derivatives
Cytosine - metabolism
DNA - metabolism
DNA Topoisomerases, Type I - metabolism
Humans
Methylcytosine
Molecular Sequence Data
SDS, sodium dodecyl sulphate
Structure-Activity Relationship
Topoisomerase
title Substitution of 5-methylcytosines for cytosines enhances the stability of topoisomerase I-DNA complexes and modulates the sequence selectivity of camptothecin-induced DNA cleavage
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