Abnormal expression of the nuclear-associated enzyme DNA topoisomerase II (topoisomerase II) has been implicated in the in vitro phenotype of radiation hypersensitive ataxia-telangiectasia (A-T) cells and in modifying sensitivity of eukaryotic cells to topoisomerase II-inhibitor drugs [e.g., the DNA intercalator amsacrine (mAMSA)]. To study such relationships, various SV40- and Epstein-Barr Vir...

Anilino analogues of amsacrine showed increased activity against amsacrine (AMSA)-resistant cell lines when compared with the parent compound, but the mechanisms of amsacrine resistance in these lines wereunknown(Finlay, G. J., Baguley,B. C., Snow,K., and Judd, W., J. NatI. Cancer Inst., 82: 662—667, 1990). We tested the cytotoxic and DNA-cleaving activities of two amsacrine analogues which w...

Leishmania donovani topoisomerase I is an unusual bi-subunit enzyme. We have demonstrated earlier that the large and small subunit could be reconstituted in vitro to show topoisomerase I activity. We extend our biochemical study to evaluate the role of the large subunit in topoisomerase activity. The large subunit (LdTOP1L) shows a substantial degree of homology with the core DNA binding domain...

Leishmania donovani topoisomerase I is an unusual bisubunit enzyme. We have demonstrated earlier that the large and small subunit could be reconstituted in vitro to show topoisomerase I activity. We extend our biochemical study to evaluate the role of the large subunit in topoisomerase activity. The large subunit (LdTOP1L) shows a substantial degree of homology with the core DNA binding domain ...

The DNA-intercalating antitumor drug NB-506 is a potent topoisomerase poison currently undergoing phase I/II clinical trials. It contains a planar indolocarbazole chromophore substituted with a glucose residue. Up until now, it was thought that intercalation of the drug into DNA was essential for the stabilization of topoisomerase I-DNA covalent complexes. But, in the present study, we show tha...

The intracellular level of DNA topoisomerase II appears to be reversibly regulated by serum concentration in cultured primary human skin fibroblasts (HSF). Upon serum starvation, the intracellular level of topoisomerase II in HSF, as monitored by immunoblotting with antitopoisomerase II antibodies, gradually decreased to a nondetectable level (less than 10(4) copies/cell) over a period of 72 h....

Moxifloxacin has enhanced potency against Staphylococcus aureus, lower propensity to select for resistant mutants, and higher bactericidal activity against highly resistant strains than ciprofloxacin. Despite similar activity against purified S. aureus topoisomerase IV and DNA gyrase, it selects for topoisomerase IV mutants, making topoisomerase IV the preferred target in vivo.

Targeted disruption of the mouse TOP3a gene encoding DNA topoisomerase IIIa was carried out to study the physiological functions of the mammalian type IA DNA topoisomerase. Whereas heterozygous top3a1/2 mutant mice were found to resemble phenotypically their TOP3a1/1 litermates, no viable top3a2/2 homozygotes were found among over 100 progeny of top3a1/2 intercrosses. Examination of embryos dis...

T^pe II DNA topoisomerase breaks both DNA strands, and many anticancer agents including etoposide (VP-16) and teniposide (VM-26) have been developed by targeting topoisomerase II molecules. In this study we examined whether expression of the topoisomerase II gene is regulated in response to heat shock stress in human epidermoid cancer KB cells. Exposure of KB cells to 42°Cfor 3 to 24 h permitt...

DNA topoisomerases contribute to various cellular activities that involve DNA. We previously identified a human nuclear gene that encodes a mitochondrial DNA topoisomerase. Here we show that genes for mitochondrial DNA topoisomerases (type IB) exist only in vertebrates. A 13-exon topoisomerase motif was identified as a characteristic of genes for both nuclear and mitochondrial type IB topoisome...