INFLUENCE OF ELSAMICIN-A ON THE ACTIVITY OF MAMMALIAN TOPOISOMERASE-I

Citation
A. Rodriguezcampos et al., INFLUENCE OF ELSAMICIN-A ON THE ACTIVITY OF MAMMALIAN TOPOISOMERASE-I, Biochemistry, 35(34), 1996, pp. 11177-11182
Citations number
23
Categorie Soggetti
Biology
Journal title
ISSN journal
00062960
Volume
35
Issue
34
Year of publication
1996
Pages
11177 - 11182
Database
ISI
SICI code
0006-2960(1996)35:34<11177:IOEOTA>2.0.ZU;2-D
Abstract
The strong effect of elsamicin A on the mobility of DNA in agarose gel s has been characterized, This antibiotic forms tight complexes that a re resistant to an electrophoretic field, though they are not covalent and can be removed by phenol or I-butanol extraction, In the presence of mammalian topoisomerase I, elsamicin A behaves as an intercalating agent in unwinding experiments performed with either phi X174 rf I (d ouble-stranded, covalently closed DNA) or relaxed pUC19. The unwinding assay was used to calculate the apparent unwinding angle per bound an tibiotic molecule, phi = 19 +/- 2.7 degrees. Moreover, an apparent bin ding constant for elsamicin was derived, under the experimental condit ions of the topoisomerase I assays, using the Scatchard equation, The effects of elsamicin A on the mammalian topoisomerase I catalytic cycl e do not seem to involve inhibition of the enzyme. Neither symptoms of trapping of covalent DNA-topoisomerase I cleavable complexes nor ''no nspecific'' inhibition, based solely on DNA binding, was apparent. Uti lizing an experimental approach based on the use of relaxed plasmid DN A, we suggest that elsamicin might not be a topoisomerase I inhibitor.