The essential role of yeast topoisomerase III in meiosis depends on recombination

Abstract

Yeast cells mutant for TOP3, the gene encoding the evolutionary conserved type I-5Ј topoisomerase, display a wide range of phenotypes including altered cell cycle, hyper-recombination, abnormal gene expression, poor mating, chromosome instability and absence of sporulation. In this report, an analysis of the role of TOP3 in the meiotic process indicates that top3Δ mutants enter meiosis and complete the initial steps of recombination. However, reductional division does not occur. Deletion of the SPO11 gene, which prevents recombination between homologous chromosomes in meiosis I division, allows top3Δ mutants to form viable spores, indicating that Top3 is required to complete recombination successfully. A topoisomerase activity is involved in this process, since expression of bacterial TopA in yeast top3Δ mutants permits sporulation. The meiotic block is also partially suppressed by a deletion of SGS1, a gene encoding a helicase that interacts with Top3. We propose an essential role for Top3 in the processing of molecules generated during meiotic recombination.

Multiple Genetic Pathways Involving the Caenorhabditis elegans Bloom's Syndrome Genes him-6, rad-51, and top-3 Are Needed To Maintain Genome Stability in the Germ Line

“…Indeed, we also observed a similar defect in irradiated rad-51 and mre-11 worms in which massive levels of double-strand breaks are generated but cannot be repaired (A. Gartner and A. Alpi, unpublished observations). Our finding thus generalizes observations made in yeast, suggesting that top-3 might be required during meiosis in a stage acting after the initiation of meiotic double-strand breaks (16).…”

“…In S. cerevisiae, the single RecQ homolog (Sgs1p) is not required for the initiation of doublestrand breaks but seems to be needed for the processing of recombination intermediates during meiosis. The first meiotic division in sgs1 mutant is delayed, and this delay is alleviated in a spo11-deficient background (16). More recently, Sgs1p was shown to regulate chromosome synapsis and meiotic crossingover (45).…”

“…Sgs1p acts redundantly with the budding yeast helicase Srs2p, which has been shown to inhibit loading of Rad51p onto single-stranded DNA (ssDNA) in vitro (33,56). In addition, the sgs1 mutants display some meiotic defects such as delayed meiotic prophase and defective chromosome synapsis (16,45). In vitro, Sgs1p interacts physically with Top3p (17), and Sgs1p-Top3p, together with Srs2p, suppresses crossovers during double-strand break repair (25).…”

Top3 Processes Recombination Intermediates and Modulates Checkpoint Activity after DNA Damage

“…Of the three topoisomerases in yeast, the function(s) of the sole type IA topoisomerase, Top3, remains most poorly understood. However, it is likely that Top3 fulfills important roles in vivo, because deletion of TOP3 in Saccharomyces cerevisiae causes hyperrecombination, sensitivity to genotoxic agents, meiotic defects, and poor growth due to accumulation of cells with a late S/G 2 content of DNA (Wallis et al, 1989;Gangloff et al, 1994Gangloff et al, , 1999Chakraverty et al, 2001). Similarly, deletion of top3 ϩ in Schizosaccharomyces pombe causes lethality due to chromosome missegregation and accumulation of DNA double-strand breaks (Goodwin et al, 1999;Maftahi et al, 1999;Oh et al, 2002;Win et al, 2004).…”

Infertility and aneuploidy in mice lacking a type IA DNA topoisomerase IIIβ

“…Whereas sporulation of Saccharomyces cerevisiae top3 diploids yields no viable spores, this lethality can be prevented by blocking meiotic recombination (7). Concordantly, inactivation of the E. coli recA gene, which is essential for homologous recombination, restores viability of a topA topB double mutant lacking both DNA topoisomerases I and III (4).…”