Nucleic Acids Research, Vol 27, Issue 20 4050-4058, Copyright © 1999 by Oxford University Press
A Goodwin, SW Wang, T Toda, C Norbury and ID Hickson
Topoisomerases catalyse changes in the topological state of DNA and are
required for many aspects of DNA 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 yeast 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 late stage replicons to permit faithful
chromosome segregation during anaphase.
ARTICLES
Topoisomerase III is essential for accurate nuclear division in Schizosaccharomyces pombe
Imperial Cancer Research Fund Laboratories, London, UK.
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