In the late 1980s, reports emerged describing experimental antibacterial quinolones having significant potency against eukaryotic Type II topoisomerases (topo II) and showing cytotoxic activity against tumor cell lines. As a result, several pharmaceutical companies initiated quinolone anticancer programs to explore the potential of this class in comparison to conventional human topo II inhibiti...

BLM, a RecQ family DNA helicase mutated in Bloom's Syndrome, participates in homologous recombination at two stages: 5' DNA end resection and double Holliday junction dissolution. BLM exists in a complex with Topo IIIα, RMI1 and RMI2. Herein, we address the role of Topo IIIα and RMI1-RMI2 in resection using a reconstituted system with purified human proteins. We show that Topo IIIα stimulates D...

Systemic sclerosis (SSc) is an autoimmune connective tissue disease of unknown etiology in which T cell responses to various autoantigens, including DNA topoisomerase I (Topo I), have been implicated. We investigated whether dendritic cells, generally considered to be the most potent APCs for the initiation of immune responses, would present either of two forms of Topo I to T cells more efficie...

Mammalian cells contain two distinct types of topoisomerases. They have been mechanistically classified into a type I (topo I) and type II (topo II) enzyme. Anticancer drugs which target topo I include camptothecin, irinotecan, topotecan, and 9-aminocamptothecin. Anticancer drugs which target topo II include etoposide, mitoxantrone, teniposide, and doxorubicin. Much experimental work has indica...

DNA nano-structures present appealing new means for monitoring different molecules. Here, we demonstrate the assembly and utilization of a surface-attached double-stranded DNA catenane composed of two intact interlinked DNA nano-circles for specific and sensitive measurements of the life essential topoisomerase II (Topo II) enzyme activity. Topo II activity was detected via the numeric release ...

Type II topoisomerases (Topo II) are essential enzymes common to all organisms. Their cellular functions include maintaining the levels of chromosome supercoiling and ensuring proper segregation at cell division. Topo II performs strand passage on its substrate DNA. This action has been well characterized at the molecular level [2]. Topo II binds a dsDNA segment called the G-segment, it introdu...

AIMS The nuclear enzyme DNA topoisomerase II has been shown to be required for chromatin condensation and chromosomal segregation during mitosis; its isoform topo II alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relation of the expression of topo II alpha to the biological behaviour of conventional urinary bladder cancer. METHODS F...

There is cumulative strong evidence that diets rich in flavanols can provide certain positive health benefits, particularly with respect to the cardiovascular system. Consequently, it has been suggested that increasing one's dietary intake of flavanols may be of benefit. Complicating this idea, there are reports that high intakes of certain flavonoids during pregnancy are associated with an inc...

BACKGROUND The unfolded protein response (UPR) is regulated by three ER-localized, transmembrane signal transducers that control distinct aspects of the UPR. We previously reported that both increased resistance to etoposide and a reduction in Topoisomerase IIα protein levels were a direct response of UPR activation, and the latter occurred independent of changes in Topo IIα mRNA levels. We hav...

Topoisomerase I (Topo I) is overexpressed in cancer colon tissues compared with normal colon tissues. Several anti-Topo I inhibitors are already successfully used in the clinic. We illustrate here the antiproliferative activity of a new class of Topo I inhibitors, i.e., E-ring-modified camptothecins with enhanced lactone stability (L. Lesueur-Ginot et al., Cancer Res., 59: 2939-2943, 1999). For...