Phosphorylation of the C-terminal Domain of Yeast Topoisomerase II by Casein Kinase II Affects DNA-Protein Interaction

Dang, Qi; Alghisi, Gian-Carlo; Gasser, Susan M.

doi:10.1006/jmbi.1994.1626

Cited by 29 publications

(13 citation statements)

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“…To mapped the sites of modification to the C-terminal domain Dang et al, 1994;Alghisi et al, 1994 Figure 7 shows the distribution of the mutant and wild-type TOP2 proteins, as detected by indirect immunofluorescence. Because our antibodies cannot distinguish between truncated and wild-type topoisomerase II forms, we always detect low-level immunofluorescence of the endogenous, exclusively nuclear wild-type enzyme (see Figure 7a; Klein et al, 1992).…”

Section: Resultsmentioning

confidence: 99%

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

Vassetzky¹,

Alghisi²,

Roberts³

et al. 1996

Br J Cancer

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Section: Resultsmentioning

confidence: 99%

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

Vassetzky¹,

Alghisi²,

Roberts³

et al. 1996

Br J Cancer

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“…It was thought that the decrease in rate at high DNA concentrations could be due to inhibition of the enzyme by binding of a third section of DNA to the enzyme, possibly at the C terminus. This region is thought to be important in enzyme cellular location, in structural roles, and in the regulation of catalytic activity, possibly by controlling enzyme-DNA interactions (49,50). Our studies with a C-terminal deletion mutant of the yeast enzyme showed that it also showed spike characteristics similar to the wild-type enzyme (data not shown), which argues against the C terminus being involved in decreasing DNA-stimulated ATPase rate by binding a third DNA segment.…”

Section: Discussionmentioning

confidence: 99%

The DNA Dependence of the ATPase Activity of Human DNA Topoisomerase IIα

Hammonds

Maxwell

1997

Journal of Biological Chemistry

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We have purified human topoisomerase II␣ from HeLa cells and studied its ATPase reaction. The ATPase activity is stimulated by DNA and shows apparent MichaelisMenten kinetics. Although the ATPase activity of human topoisomerase II␣ is lower than that of Saccharomyces cerevisiae, it is more active in decatenation, implying more efficient coupling of the ATPase to DNA strand passage under these conditions. Using plasmid pBR322 as the DNA cofactor, the reaction shows hyperstimulation by DNA at a base pair to enzyme dimer ratio of 100 -200:1. When DNA fragments are used as the cofactor, the reaction requires >ϳ ϳ100 base pairs to stimulate the activity and fragments of ϳ ϳ300 base pairs show hyperstimulation. This behavior can be rationalized in terms of the enzyme requiring fragments that can bind to both the DNA gate and the ATP-operated clamp in order for the ATPase reaction to be stimulated. Hyperstimulation is a consequence of the saturation of DNA with enzyme. The mechanistic implications of these results are discussed.DNA topoisomerases are enzymes that catalyze topological changes in DNA (1, 2). These enzymes have been found in all cell types and are essential for cell viability. Their roles include maintenance of the level of intracellular DNA supercoiling, removing supercoils, which build up ahead of and behind transcription and replication complexes, and the decatenation of daughter chromosomes following replication. The topoisomerase reaction involves the breakage of DNA in one or both strands, the formation of protein-DNA covalent bonds, and the passage of another segment of DNA through the enzyme-stabilized break. In the case of type II enzymes, this DNA strand passage reaction generally requires the hydrolysis of ATP.As a consequence of their essential roles in cells, DNA topoisomerases have become important drug targets. For example, the prokaryotic type II enzyme DNA gyrase is the target of a range of antibacterial agents such as the quinolone and coumarin drugs (3). The eukaryotic type I enzyme, DNA topoisomerase I, is the target of the antitumor agent camptothecin, and eukaryotic topoisomerase II is the target of a variety of antitumor drugs, which include amsacrine, epipodophyllotoxins, and merbarone (4, 5). Many of these compounds (e.g. quinolones, camptothecin, amsacrine, etc.) act by stabilizing a cleavable complex between the topoisomerase and DNA, in which the enzyme is covalently linked to the DNA. Arresting of DNA replication forks by this complex is thought to initiate events that lead to cell death (5). Other topoisomerase-targeted compounds act by different mechanisms, e.g. coumarin drugs (such as novobiocin) act as competitive inhibitors of the DNA gyrase ATPase reaction (6) and ICRF-159 is thought to stabilize the eukaryotic enzyme in a closed complex incapable of catalytic activity (7).On the basis of the alignment of their amino acid sequences, DNA topoisomerases can be grouped into three subfamilies: type IA, type IB, and type II (8). All type II enzymes are evolutionarily and stru...

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“…The reduced level of topoisomerase II protein after G 2 /M is attributed to the downregulation of transcription and to the decreased stability of both its mRNA and protein (Goswami et al 1996;Heck et al 1988Heck et al , 1989Ramachandran et al 1995). When dephosphorylated, topoisomerase II from budding yeast and from Swiss 3T3 cells ceases its catalytic activity (Dang et al 1994;Saijo et al 1992). The phosphorylation of topoisomerase II in the fission yeast enhances its nuclear import (Shiozaki and Yanagida 1992).…”

Section: Introductionmentioning

confidence: 95%

Type II topoisomerase activities in both the G1 and G2/M phases of the dinoflagellate cell cycle

2005

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Dinoflagellate genomes are large (up to 200 pg) and are encoded in histoneless chromosomes that are quasi-permanently condensed. This unique combination of chromosomal characteristics presents additional topological and cell cycle control problems for a eukaryotic cell, potentially exhibiting novel regulatory requirements of topoisomerase II. The heterotrophic dinoflagellate Crypthecodinium cohnii was used in this study. The topoisomerase II activities throughout its cell cycle were investigated by DNA flow cytometry following enzyme deactivation. Fluorescence microscopy was also used for studying the chromosome morphology of the treated cells. Two classes of topoisomerase II inhibitors were applied in our study, both of which caused G1 delay as well as G2/M arrest in the C. cohnii cell cycle. At high doses, the topoisomerase poisons amsacrine and ellipticine induced DNA fragmentation in C. cohnii cells. Topoisomerase II activities, as measured by the ability to decatenate kinetoplastid DNA (kDNA), are normally detected throughout the cell cycle in C. cohnii. Our results suggest that the requirement of type II topoisomerase activities during the G1 phase of the cell cycle may relate to the unwinding of quasi-permanently condensed chromosomes for the purpose of transcription. This was also the first time that topoisomerase II activity in dinoflagellate cells was detected.

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Phosphorylation of the C-terminal Domain of Yeast Topoisomerase II by Casein Kinase II Affects DNA-Protein Interaction

Cited by 29 publications

References 0 publications

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

The DNA Dependence of the ATPase Activity of Human DNA Topoisomerase IIα

Type II topoisomerase activities in both the G1 and G2/M phases of the dinoflagellate cell cycle

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