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DNA gyrase can cleave short DNA fragments in the presence of quinolone drugs

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posted on 11.03.2015, 15:14 by Matthew E. Cove, Andrew P. Tingey, Anthony Maxwell
We have analysed the DNA cleavage reaction of DNA gyrase using oligonucleotides annealed to a singlestranded M13 derivative containing a preferred gyrase cleavage site. We find that gyrase can cleave duplexes down to ∼20 bp in size in the presence of the quinolone drugs ciprofloxacin and oxolinic acid. Ciprofloxacin shows a variation in its site specificity with an apparent preference for G bases adjacent to the cleavage sites, whereas oxolinic acid stimulates cleavage predominantly at the previously determined site. With either drug, cleavage will not occur within 6 bases from the end of a DNA duplex or a nick. We suggest that cleavage site specificity with short DNA duplexes is determined by drug-DNA interactions whereas with longer fragments the positioning effect of the DNA wrap around gyrase prescribes the site of cleavage.

Funding

MEC acknowledges Knoll Pharmaceuticals (formerly Boots) and the Leicestershire Clinical Research Committee for financial support, and APT acknowledges BBSRC and GlaxoWellcome for a CASE studentship. AM is a Lister Institute Jenner Fellow.

History

Citation

Nucleic Acids Research, 1997, Vol. 25, No. 14 2716–2722

Version

VoR (Version of Record)

Published in

Nucleic Acids Research

Publisher

Oxford University Press (OUP)

issn

0305-1048

eissn

1362-4962

Copyright date

1997

Available date

11/03/2015

Publisher version

http://nar.oxfordjournals.org/content/25/14/2716

Language

en

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