Inactivation of homologous recombination suppresses defects in topoisomerase III-deficient mutants

被引:42
作者
Oakley, TJ [1 ]
Goodwin, A [1 ]
Chakravety, RK [1 ]
Hickson, ID [1 ]
机构
[1] Univ Oxford, Weatherall Inst Mol Med, Canc Res UK Labs, John Radcliffe Hosp, Oxford OX3 9DS, England
关键词
Saccharomyces cerevisiae; TOP3; gene; homologous recombination; topoisomerase III; RecQ helicases;
D O I
10.1016/S1568-7864(02)00032-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The Saccharomyces cerevisiae TOP3 gene encodes the type IA topoisomerase (Top3p) that is highly conserved in evolution. Deletion of TOP3 leads to a reduction in cell viability, hyper-recombination between repetitive DNA sequences, and abnormalities in both cell cycle progression and responses to DNA damaging agents. Deletion of SGS1, encoding the sole RecQ family helicase in S. cerevisiae, strongly suppresses the phenotypic effects of loss of TOP3 function. Here, we show that many of the adverse phenotypic effects of TOP3 deletion can also be partially alleviated by disruption of homologous recombination (HR) functions. This genetic interaction is seen both in strains deleted for TOP3 and in wild-type strains over-expressing a dominant-negative Top3p mutant form that confers a top3-like phenotype. Moreover, we show that this genetic interaction is conserved in the distantly-related fission yeast, Schizosaccharomyces pombe. Our results implicate topoisomerase III enzymes in recombination repair events required for cellular protection against DNA damaging agents and DNA replication inhibitors. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:463 / 482
页数:20
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