THE YEAST TYPE-I TOPOISOMERASE TOP3 INTERACTS WITH SGS1, A DNA HELICASE HOMOLOG - A POTENTIAL EUKARYOTIC REVERSE GYRASE

We have previously shown that cells mutant for TOP3, it gene encoding a prokaryotic-like type I topoisomerase in Saccharomyces cerevisiae, d isplay a pleiotropic phenotype including slow growth and genome instab ility. We identified a mutation, sgs1 (slow growth suppressor), that s uppresses both the growth defect and the increased genomic instability of top3 mutants. Here we report the independent isolation of the SGS1 gene in a screen for proteins that interact with Top3. DNA sequence a nalysis reveals that the putative Sgs1 protein is highly homologous to the helicase encoded by the Escherichia coli recQ gene. These results imply that Sgs1 creates a deleterious topological substrate that Top3 preferentially resolves. The interaction of the Sgs1 helicase homolog and the Top3 topoisomerase is reminiscent of the recently described s tructure of reverse gyrase from Sulfolobus acidocaldarius, in which a type I DNA topoisomerase and a helicase-like domain are fused in a sin gle polypeptide.