Topoisomerase III is essential for accurate nuclear division in Schizosaccharomyces pombe

被引:94
作者
Goodwin, A
Wang, SW
Toda, T
Norbury, C
Hickson, ID [1 ]
机构
[1] Imperial Canc Res Fund, Oxford OX3 9DS, England
[2] Univ Oxford, John Radcliffe Hosp, Inst Mol Med, Oxford OX3 ODS, England
[3] Cell Regulat Lab, London WC2A 3PX, England
关键词
D O I
10.1093/nar/27.20.4050
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Topoisomerases catalyse changes in the topological state of DMA and are required for many aspects of PNA metabolism. While the functions of topoisomerases I and II in eukaryotes are well established, the role of topoisomerase III remains poorly defined. We have identified a gene in the fission Schizosaccharomyces pombe, designated top3(+), which shows significant sequence similarity to genes encoding topoisomerase III enzymes in other eukaryotic species. In common with murine TOP3 alpha, but in contrast to Saccharomyces cerevisiae TOP3, the S.pombe top3(+) gene is essential for long-term cell viability. Fission yeast haploid spores containing a disrupted top3(+) gene germinate successfully, but then undergo only a limited number of cell divisions. Analysis of these top3 mutants revealed evidence of aberrant mitotic chromosome segregation, including the 'cut' phenotype, where septation is completed prior to nuclear division. Consistent with the existence of an intimate association (originally identified in S.cerevisiae) between topoisomerase III and DNA helicases of the RecQ family, deletion of the rqh1(+) gene encoding the only known RecQ helicase in S.pombe suppresses lethality in top3 mutants. This conservation of genetic interaction between two widely diverged yeasts suggests that the RecQ family helicases encoded by the Bloom's and Werner's syndrome genes are likely to act in concert with topoisomerase III isozymes in human cells. Our data are consistent with a model in which the association of a RecQ helicase and topoisomerase III is important for facilitating decatenation of rate stage replicons to permit faithful chromosome segregation during anaphase.
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页码:4050 / 4058
页数:9
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