Topoisomerase II creates a double-strand break intermediate with topoisomerase covalently coupled to the DNA via a 5'-phosphotyrosyl bond. These intermediate complexes can become cytotoxic protein-DNA adducts and DSB repair at these lesions requires removal of topoisomerase II. To analyse removal of topoisomerase II from genomic DNA we adapted the trapped in agarose DNA immunostaining assay. Re...

Topoisomerase is one of the most important targets anti-cancer drugs. In order to develop effective and low-toxic topoisomerase inhibitors, a series xanthone derivatives have been designed synthesized using principles skeleton transition. vitro cytotoxicity assays human breast cancer (MCF-7), gastric (MGC-803), cervical cancer(Hela) cell lines, compounds showed antitumor growth activity, also l...

Poly(ADP-ribose) polymerase-1 (PARP-1) is known to have an important role in camptothecin sensitivity and interacts with topoisomerase I. In the present study, the impact of PARP-1 on the topoisomerase I-DNA complex stabilized by camptothecin was assessed. It was shown that NH2 terminus-truncated topoisomerase I (amino acids 201-765) showed at least 4-fold less sensitivity to camptothecin than ...

Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. A rationale for the use of sequential therapy involving the combination of camptothecins with topoisomerase II-targeting drugs, such as etoposide, has arisen from observations of increased topoiso...

Mammalian cells express two genetically distinct isoforms of DNA topoisomerase II, designated topoisomerase IIalphaand topoisomerase IIbeta. We have recently shown that mouse topoisomerase IIalpha can substitute for the yeast topoisomerase II enzyme and complement yeast top2 mutations. This functional complementation allowed functional analysis of the C-terminal domain (CTD) of mammalian topois...

Mitonafide (4-nitro-benzoisoquinolinedione) and a number of structural analogs were synthesized and studied in order to determine the structural requirements for inhibition of leishmanial nuclear and kinetoplast topoisomerase II and human topoisomerase II. The structure-activity relationship studies with the mitonafide analogs demonstrated that there was selective targeting of leishmanial nucle...

AIMS To determine, by in situ immunohistochemistry, whether ovarian carcinomas have increased expression of DNA topoisomerase I. METHODS Paraffin wax blocks obtained from 15 samples of normal human tissues and from 14 cases of ovarian cancer were cut on to glass slides and immunohistochemically stained for topoisomerase I. The primary antibody was a mouse monoclonal that recognises topoisomer...

The azafluoranthene alkaloid eupolauridine has previously been shown to have in vitro antifungal activity and selective inhibition of fungal topoisomerase I. The present study was undertaken to examine further its selectivity and mode of action. Eupolauridine completely inhibits the DNA relaxation activity of purified fungal topoisomerase I at 50 microg/ml, but it does not stabilize the cleavag...

Screening of a human B-cell cDNA library with a topoisomerase II beta gene-specific probe revealed the presence of two distinct forms of topoisomerase II beta cDNA. One form (designated topoisomerase II beta-1), representing the majority of the clones, would encode the topoisomerase II beta amino acid sequence reported recently [Jenkins, J.R. et al. (1992) Nucleic Acids Res., 20, 5587-5592]. Th...

Eukaryotic DNA topoisomerase III was first identified by studying the hyper-recombination and slow growth phenotypes of yeast mutants. Topoisomerase III interacts with DNA helicase SGS1 and the two proteins are involved in DNA recombination, cellular aging and maintenance of genome stability. A human homolog of topoisomerase III has previously been identified. Here we report the identification ...