DNA topoisomerases are nuclear enzymes inducing transient breaks in the DNA allowing DNA strands or double helices to pass through each other. The clinically used DNA topoisomerase II-poison etoposide is known to induce DNA double strand breaks leading to chromosomal aberrations and leukemias. Recently, some alarming studies have been published, suggesting that maternal exposure to low doses of...

The relationship between DNA topoisomerase II activity and drug resistance was studied in cloned cell lines of Adriamycin (ADR)-sensitive and -resistant P388 leukemia; drug resistant P388/ADR/3 (clone 3) and P388/ADR/7 (clone 7) cells are 5- and 10-fold more resistant to ADR than the sensitive cell line P388/4 (Cancer Res., 46: 2978, 1986). Topoisomerase II catalytic activity in crude nuclear e...

We examined the effects of phorbol ester treatment on topoisomerase II-mediated events in two human leukemia cell lines with different proclivities toward phorbol ester-induced monocytoid differentiation. HL-60 is the parent line that will terminally differentiate; 1E3 is a derived line that will not terminally differentiate. Within 24 h of phorbol ester treatment, etoposide-induced, topoisomer...

A new multiple drug-resistant Chinese hamster ovary cell line, ( IK )SMRs, has been isolated which demonstrates a direct correlation between reduced cellular topoisomerase II activity (5-fold reduction) and a low level of resistance (3to 7-fold) to topoisomerase II inhibitors. This cell line, initially selected for resistance to 9-(4,6-0-ethylidene-i8-D-glucopyranosyl)-4'-demethylepipodophyllot...

Bulgarein, a fungal metabolite, induced mammalian topoisomerase I-mediated DNA cleavage in vitro. The cleavage activity of bulgarein was comparable to that of camptothecin at a drug concentration range of 0.025-approximately 5 microM. The DNA cleavage induced by bulgarein was suppressed at concentrations above 12.5 microM. Treatment of a reaction mixture containing bulgarein and topoisomerase I...

Poly(ADP-ribose) polymerase (PARP)-1 was reported to promote the religation activity of topoisomerase I in the presence of camptothecin by itself through the direct interaction with topoisomerase I or by the formation of poly(ADP-ribosyl)ated topoisomerase I. We have demonstrated previously that ATP inhibited PARP-1/NAD-facilitated religation of topoisomerase I-linked DNA (TLD) in the presence ...

DNA topoisomerase I from Mycobacterium smegmatis unlike many other type I topoisomerases is a site specific DNA binding protein. We have investigated the sequence specific DNA binding characteristics of the enzyme using specific oligonucleotides of varied length. DNA binding, oligonucleotide competition and covalent complex assays show that the substrate length requirement for interaction is mu...

We demonstrate that the topoisomerase activity of bacteriophage lambda Int protein introduces single-strand breaks into duplex DNA at specific sites. Strand breakage is accompanied by the covalent linkage of Int to DNA. The linkage connects a residue in Int to the 3' phosphate of DNA at the site of breakage; the other breakage product has a 5' OH terminus. Int is the first procaryotic topoisome...

Tn5 transposase (Tnp) overproduction is lethal to Escherichia coli. The overproduction causes cell filamentation and abnormal chromosome segregation. Here we present three lines of evidence strongly suggesting that Tnp overproduction killing is due to titration of topoisomerase I. First, a suppressor mutation of transposase overproduction killing, stkD10, is localized in topA (the gene for topo...

Topoisomerase II, purified from chicken erythrocytes, was reacted with a large number of different DNA fragments and cleavages were catalogued in the presence and absence of drugs that stabilize the cleavage intermediate. Cleavages were sequenced to derive a consensus for topoisomerase II that predicts catalytic sites. The consensus is: (sequence; see text) where N is any base and cleavage occu...