Functional compatibility between isoform α and β of type II DNA topoisomerase

Sakaguchi, Ayako; Kikuchi, Akihiko

doi:10.1242/jcs.00977

Cited by 94 publications

(104 citation statements)

References 26 publications

(26 reference statements)

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“…In the absence of suitable topoII mutants, in vivo studies in higher eukaryotes have made use of topoII inhibitors (Andoh et al, 1993;Downes et al, 1994;Gorbsky, 1994;Ishida et al, 1994;Gimenez-Abian et al, 1995;Andreassen et al, 1997;Gimenez-Abian et al, 2000) or RNA interference (Chang et al, 2003;Sakaguchi and Kikuchi, 2004). Such studies mostly support a role for topoII in chromosome condensation, but again, condensation was impaired to varying degrees, and in some cases (Andreassen et al, 1997;Chang et al, 2003;Sakaguchi and Kikuchi, 2004) impairment was surprisingly mild or absent. Thus, although both structural (Mirkovitch et al, 1988;Hart and Laemmli, 1998) and catalytic (Koshland and Strunnikov, 1996;Hirano, 2000) models for how topoII may be involved in chromosome condensation have been proposed, the issue of whether topoII is required for condensation remains controversial.…”

Section: Introductionmentioning

confidence: 99%

“…In vitro studies of chromosome condensation in mitotic extracts (Newport and Spann, 1987;Adachi et al, 1991;Hirano and Mitchison, 1991, 1993), in which topoII is immunodepleted or inactivated by inhibitors, showed varying requirements for topoII. In the absence of suitable topoII mutants, in vivo studies in higher eukaryotes have made use of topoII inhibitors (Andoh et al, 1993;Downes et al, 1994;Gorbsky, 1994;Ishida et al, 1994;Gimenez-Abian et al, 1995;Andreassen et al, 1997;Gimenez-Abian et al, 2000) or RNA interference (Chang et al, 2003;Sakaguchi and Kikuchi, 2004). Such studies mostly support a role for topoII in chromosome condensation, but again, condensation was impaired to varying degrees, and in some cases (Andreassen et al, 1997;Chang et al, 2003;Sakaguchi and Kikuchi, 2004) impairment was surprisingly mild or absent.…”

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confidence: 99%

“…Third, conditional mutagenesis allows complementation studies to be done. Although RNA interference can be used to deplete individual topoII isoforms (Sakaguchi and Kikuchi, 2004), this approach has not yet been applied to topoII in a way that avoids significant residual expression or allows for complementation analyses. Complementation would be particularly valuable for the analysis of the numerous phosphoryation sites in topoII␣, which have variously been implicated in controlling topoII␣ activity, resistance to inhibition, and subcellular localization, but whose true physiological significance remains untested (Isaacs et al, 1998;Chikamori et al, 2003).…”

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confidence: 99%

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Construction, Characterization, and Complementation of a Conditional-Lethal DNA Topoisomerase IIα Mutant Human Cell Line

Carpenter

Porter

2004

MBoC

136

175

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DNA Topoisomerase II␣ (topoII␣) is a DNA decatenating enzyme, abundant constituent of mammalian mitotic chromosomes, and target of numerous antitumor drugs, but its exact role in chromosome structure and dynamics is unclear. In a powerful new approach to this important problem, with significant advantages over the use of topoII inhibitors or RNA interference, we have generated and characterized a human cell line (HTETOP) in which >99.5% topoII␣ expression can be silenced in all cells by the addition of tetracycline. TopoII␣-depleted HTETOP cells enter mitosis and undergo chromosome condensation, albeit with delayed kinetics, but normal anaphases and cytokineses are completely prevented, and all cells die, some becoming polyploid in the process. Cells can be rescued by expression of topoII␣ fused to green fluorescent protein (GFP), even when certain phosphorylation sites have been mutated, but not when the catalytic residue Y805 is mutated. Thus, in addition to validating GFP-tagged topoII␣ as an indicator for endogenous topoII␣ dynamics, our analyses provide new evidence that topoII␣ plays a largely redundant role in chromosome condensation, but an essential catalytic role in chromosome segregation that cannot be complemented by topoII␤ and does not require phosphorylation at serine residues 1106, 1247, 1354, or 1393. INTRODUCTIONType II topoisomerases are ubiquitous, highly conserved proteins that catalyze the passage of one DNA duplex through another, creating a transient double-strand break (DSB) in the latter (Watt and Hickson, 1994;Wang, 2002). Studies in a variety of systems indicate that topoII is essential for cellular viability and that it plays a key role in chromosome segregation. Thus, the abnormal cell divisions seen in yeast top2 mutants (Holm et al., 1985;Uemura and Yanagida, 1986), and in vertebrate cells treated with topoII inhibitors (Downes et al., 1991;Ishida et al., 1991Ishida et al., , 1994Haraguchi et al., 2000) are consistent with the unique ability of topoII to resolve the sister chromatids catenations generated when DNA replication forks meet (Wang, 2002). TopoII has been implicated in mammalian centromere function (Floridia et al., 2000;Spence et al., 2002), and it has been suggested that topoII in yeast may play a role in centromeric chromatin structure (Bachant et al., 2002). Further work is required to understand the relationship between any such structural role, topoII-mediated chromatid decatenation, and the role of the cohesin complex (Nasmyth, 2002) in maintaining sister chromatid cohesion until anaphase (Bernard and Allshire, 2002).TopoII also has been implicated in DNA recombination, replication, transcription, and chromosome condensation (Watt and Hickson, 1994;Wang, 2002). Of these, chromosome condensation is the only process in which topoII is widely reported to play an essential role (Koshland and Strunnikov, 1996;Losada and Hirano, 2001;Swedlow and Hirano, 2003), but the data are equivocal. Genetic analyses suggest that topoII is required for chromosome condensation in Sc...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Construction, Characterization, and Complementation of a Conditional-Lethal DNA Topoisomerase IIα Mutant Human Cell Line

Carpenter

Porter

2004

MBoC

136

175

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“…Genetic studies using model organisms as well as RNA interference (RNAi)-mediated gene silencing analyses using human cell lines indicated that DNA topoisomerase II (topoII) and a protein complex termed condensin play a crucial role in the process of mitotic chromosomal condensation. [1][2][3] Inhibition or depletion of these molecules induces chromosomal mis-segregation and subsequent tetraploidy. [2][3][4] Such tetraploid errors were revealed to occur spontaneously in growing cells and facilitate tumor development.…”

mentioning

confidence: 99%

“…[1][2][3] Inhibition or depletion of these molecules induces chromosomal mis-segregation and subsequent tetraploidy. [2][3][4] Such tetraploid errors were revealed to occur spontaneously in growing cells and facilitate tumor development. [5][6][7] Therefore, such dangerous tetraploid cells should not progress through the cell cycle and should be eliminated in vivo.…”

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confidence: 99%

Novel cell death by downregulation of eEF1A1 expression in tetraploids

Kobayashi

Yonehara

2008

Cell Death Differ

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When duplicated sister chromatids are not properly compacted in mitosis, chromosomes are mis-segregated, inducing genetically unstable tetraploidy known to facilitate aneuploid malignancies. Here, we show that tetraploid cells produced by impaired chromosomal condensation are eliminated by a novel type of cell death different from caspase-dependent apoptosis. The cell death was associated with downregulation of eukaryotic translation elongation factor-1 a 1 (eEF1A1/EF-1a) expression in conjunction with accumulation of its mRNA in processing bodies (P bodies). Importantly, expression of exogenous eEF1A1 was shown to inhibit the caspase-independent cell death, and a similar cell death was observed after inducing the expression of short hairpin RNA specific for eEF1A1. Furthermore, the number of spontaneously arising binucleated cells was indicated to increase several fold during 1-to 2-week cultivation after initiation of exogenous eEF1A expression. Taken together, the novel cell death machinery should help to eliminate abnormal tetraploid cells and inhibit tumorigenesis.

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In vitro long‐term repeated exposure and exposure switching of a novel tobacco vapor product in a human organotypic culture of bronchial epithelial cells

Ito

Matsumura

Ishimori

et al. 2020

J of Applied Toxicology

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Next‐generation tobacco products and nicotine delivery systems such as heat‐not‐burn tobacco products and electronic cigarettes, the usage of which is expected to have a beneficial impact on public health, have gained popularity over the past decade. However, the risks associated with the long‐term use of such products are still incompletely understood. Although the risks of these products should be clarified through epidemiological studies, such studies are normally performed based on each product category, not product‐by‐product. Therefore, investigation of the risk on a product‐by‐product basis is important to provide specific scientific evidence. In the current study, we performed the 40‐day repeated exposure of in vitro human bronchial epithelial tissues to cigarette smoke (CS) or vapor from our proprietary novel tobacco vapor product (NTV). In addition, tissue samples exposed to CS were switched to NTV or CS exposure was stopped at 20 days to reflect a situation where smokers switched to NTV or ceased to smoke. All tissue samples were assessed in terms of toxicity, inflammation and transcriptomic alterations. Tissue samples switched to NTV and the cessation of exposure samples showed recovery from CS‐induced damage although there was a time‐course difference. Moreover, repeated exposure to NTV produced negligible effects on the tissue samples while CS produced cumulative effects. Our results suggest that the use of NTV, including switching to NTV from cigarette smoking, has fewer effects on bronchial epithelial tissues than continuing smoking.

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Functional compatibility between isoform α and β of type II DNA topoisomerase

Cited by 94 publications

References 26 publications

Construction, Characterization, and Complementation of a Conditional-Lethal DNA Topoisomerase IIα Mutant Human Cell Line

Construction, Characterization, and Complementation of a Conditional-Lethal DNA Topoisomerase IIα Mutant Human Cell Line

Novel cell death by downregulation of eEF1A1 expression in tetraploids

In vitro long‐term repeated exposure and exposure switching of a novel tobacco vapor product in a human organotypic culture of bronchial epithelial cells

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