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

FEBS Letters

Waring, Michael J²  Bailly, Christian¹  Carrasco, Carolina¹ 

[1] Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret et INSERM U-124, IRCL, Place de Verdun, 59045 Lille Cedex, France;Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK

关键词: Topoisomerase;    Methylcytosine;    Camptothecin;    SDS;    sodium dodecyl sulphate;   

DOI  :  10.1016/S0014-5793(98)00259-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown