Similar sequence specificity of mitoxantrone and VM-26 stimulation of in vitro DNA cleavage by mammalian DNA topoisomerase II

Biochemistry ◽  
1993 ◽  
Vol 32 (12) ◽  
pp. 3038-3046 ◽  
Author(s):  
Giovanni Capranico ◽  
Paola De Isabella ◽  
Stella Tinelli ◽  
Mario Bigioni ◽  
Franco Zunino
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Sequence Specificity ◽  
Dna Topoisomerase Ii ◽  
Similar Sequence ◽  
Dna Topoisomerase ◽  
Stimulation Of

The in vivo distribution and dynamics of DNA topoisomerase II in Drosophila embryonic nuclei and chromosomes

1993 ◽  
Vol 51 ◽  
pp. 74-75
Author(s):  
Jason R. Swedlow ◽  
Neil Osheroff ◽  
Tim Karr ◽  
John W. Sedat ◽  
David A. Agard
Keyword(s):  
Topoisomerase Ii ◽  
Biochemical Characterization ◽  
Developmental Cycle ◽  
Dna Topoisomerase Ii ◽  
Chromosomal Distribution ◽  
Dna Topoisomerase ◽  
Ideal System ◽  
Dnase Treatment

DNA topoisomerase II is an ATP-dependent double-stranded DNA strand-passing enzyme that is necessary for full condensation of chromosomes and for complete segregation of sister chromatids at mitosis in vivo and in vitro. Biochemical characterization of chromosomes or nuclei after extraction with high-salt or detergents and DNAse treatment showed that topoisomerase II was a major component of this remnant, termed the chromosome scaffold. The scaffold has been hypothesized to be the structural backbone of the chromosome, so the localization of topoisomerase II to die scaffold suggested that the enzyme might play a structural role in the chromosome. However, topoisomerase II has not been studied in nuclei or chromosomes in vivo. We have monitored the chromosomal distribution of topoisomerase II in vivo during mitosis in the Drosophila embryo. This embryo forms a multi-nucleated syncytial blastoderm early in its developmental cycle. During this time, the embryonic nuclei synchronously progress through 13 mitotic cycles, so this is an ideal system to follow nuclear and chromosomal dynamics.

Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26

Biochemistry ◽  
1988 ◽  
Vol 27 (24) ◽  
pp. 8861-8869 ◽  
Author(s):  
Mary K. Danks ◽  
Carla A. Schmidt ◽  
Margaret C. Cirtain ◽  
D. Parker Suttle ◽  
William T. Beck
Keyword(s):  
Catalytic Activity ◽  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Leukemic Cells ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Human Leukemic Cells

The C-terminal domain of Saccharomyces cerevisiae DNA topoisomerase II

1994 ◽  
Vol 14 (5) ◽  
pp. 3197-3207
Author(s):  
P R Caron ◽  
P Watt ◽  
J C Wang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Nuclear Localization ◽  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Mutant Proteins ◽  
Terminal Domain ◽  
Catalytically Active

A set of carboxy-terminal deletion mutants of Saccharomyces cerevisiae DNA topoisomerase II were constructed for studying the functions of the carboxyl domain in vitro and in vivo. The wild-type yeast enzyme is a homodimer with 1,429 amino acid residues in each of the two polypeptides; truncation of the C terminus to Ile-1220 has little effect on the function of the enzyme in vitro or in vivo, whereas truncations extending beyond Gln-1138 yield completely inactive proteins. Several mutant enzymes with C termini in between these two residues were found to be catalytically active but unable to complement a top2-4 temperature-sensitive mutation. Immunomicroscopy results suggest that the removal of a nuclear localization signal in the C-terminal domain is likely to contribute to the physiological dysfunction of these proteins; the ability of these mutant proteins to relax supercoiled DNA in vivo shows, however, that at least some of the mutant proteins are present in the nuclei in a catalytically active form. In contrast to the ability of the catalytically active mutant proteins to relax supercoiled intracellular DNA, all mutants that do not complement the temperature-dependent lethality and high frequency of chromosomal nondisjunction of top2-4 were found to lack decatenation activity in vivo. The plausible roles of the DNA topoisomerase II C-terminal domain, in addition to providing a signal for nuclear localization, are discussed in the light of these results.

scholarly journals Coupling between ATP Binding and DNA Cleavage by DNA Topoisomerase II

2008 ◽  
Vol 283 (25) ◽  
pp. 17463-17476 ◽  
Author(s):  
Felix Mueller-Planitz ◽  
Daniel Herschlag
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
Atp Binding ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase

Tannins as Potent Inhibitors of DNA Topoisomerase II In Vitro

1993 ◽  
Vol 82 (5) ◽  
pp. 487-492 ◽  
Author(s):  
Yoshiki Kashiwada ◽  
Gen-Ichiro Nonaka ◽  
Itsuo Nishioka ◽  
Kenneth Jiann-Hung Lee ◽  
Ibrahim Bori ◽  
...  
Keyword(s):  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase

scholarly journals Antimalarial 9-Anilinoacridine Compounds Directed at Hematin

2003 ◽  
Vol 47 (12) ◽  
pp. 3708-3712 ◽  
Author(s):  
Saranya Auparakkitanon ◽  
Wilai Noonpakdee ◽  
Raymond K. Ralph ◽  
William A. Denny ◽  
Prapon Wilairat
Keyword(s):  
Topoisomerase Ii ◽  
Rapid Onset ◽  
Stoichiometric Ratio ◽  
The Novel ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Molar Ratios ◽  
Low Concentrations ◽  
Absorbance Changes

ABSTRACT Antimalarial 9-anilinoacridines are potent inhibitors of parasite DNA topoisomerase II both in vitro and in situ. 3,6-Diamino substitution on the acridine ring greatly improves parasiticidal activity against Plasmodium falciparum by targeting DNA topoisomerase II. A series of 9-anilinoacridines were investigated for their abilities to inhibitβ -hematin formation, to form drug-hematin complexes, and to enhance hematin-induced lysis of red blood cells. Inhibition ofβ -hematin formation was minimal with 3,6-diamino analogs of 9-anilinoacridine and greatest with analogs with a 3,6-diCl substitution together with an electron-donating group in the 1′-anilino position. On the other hand, the presence of a 1′-N(CH3)2 group in the anilino ring produced compounds that strongly inhibited β-hematin formation but which did not appear to be sensitive to the nature of the substitutions in the acridine nucleus. The derivatives bound hematin, and Job's plots of UV-visible absorbance changes in drug-hematin complexes at various molar ratios indicated a stoichiometric ratio of 1:2. The drugs enhanced hematin-induced red blood cell lysis at low concentrations (<4 μM). These studies open up the novel possibility of development of 9-anilinoacridine antimalarials that target not only DNA topoisomerase II but alsoβ -hematin formation, which should help delay the rapid onset of resistance to drugs acting at only a single site.

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