Inactivation of homologous recombination suppresses defects in topoisomerase III-deficient mutants.
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.
Oakley
Thomas J
TJ
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Goodwin
Adele
A
Chakraverty
Ronjon K
RK
Hickson
Ian D
ID
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D018797:Cell Cycle Proteins; D002470:Cell Survival; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D015966:Gene Expression Regulation, Fungal; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D053484:RecQ Helicases; D011995:Recombination, Genetic / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D017384:Sequence Deletion; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; D004265:DNA Helicases; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I