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Nucleic Acids Research, 1992, Vol. 20, No. 5 983-990
© 1992

CHEMISTRY

Evidence for cross-linking DNA by bis-intercalators with rigid and extended linkers is provided by knotting and catenation

Nikoi K. Annan, Peter R. Cook1, Stephen T. Mullins2 and Gordon Lowe*

Dyson Perrins Laboratory, Oxford University South Parks Road, Oxford 0X1 3QY 1Sir William Dunn School of Pathology, Oxford University South Parks Road, Oxford 0X1 3RE 2Department of Chemistry, Brunei University Uxbridge, Middlesex UB8 3PH, UK

*To whom correspondence should be addressed

Received January 9, 1992. Revised February 5, 1992. Accepted February 5, 1992.

A new series of DNA bis-intercalators is reported in which acridine moieties are connected by rigid and extended pyridine-based linkers of varied length. Cross-linking of DNA by bis-intercalation is inferred from the unwinding and folding of linear DNA induced by the compounds; after Ikjation and removal of the bis-intercalator, superhelical circles, catenanes and knots that bear a residual imprint of the bis-intercalator are observed. These novel bis-intercalators are of interest because they can be used to probe the spatial organization of DNA, especially near sites of replication, recombination or topoisomerase action where two duplexes must be in close proximity. Preliminary results on the effects of the various compounds on the cloning efficiency of bacteria and replication by permeabillzed human cells are also presented.


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