Mus81/Mms4 endonuclease and Sgs1 helicase collaborate to ensure proper recombination intermediate metabolism during meiosis.
Budding yeast lacking the Sgs1 helicase and the Mus81/Mms4 endonuclease are inviable, and indirect studies implicate homologous recombination gone awry as the cause of death. We show that mutants lacking both enzymes have profound defects in meiotic recombination intermediate metabolism and crossover (CO) formation. Recombination intermediates (joint molecules, JMs) accumulate in these cells, many with structures that are infrequent in wild-type cells. These JMs persist, preventing nuclear division. Using an inducible expression system, we restored Mus81 or Sgs1 to sgs1 mus81 cells at a time when JMs are forming. Mus81 expression did not prevent JM formation but did restore JM resolution, CO formation, and nuclear division. In contrast, Sgs1 expression reduced the extent of JM accumulation. These results indicate that Sgs1 and Mus81/Mms4 collaborate to direct meiotic recombination toward interhomolog interactions that promote proper chromosome segregation, and also indicate that Mus81/Mms4 promotes JM resolution in vivo.
Jessop
Lea
L
Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4260, USA.
Lichten
Michael
M
D002467:Cell Nucleus / Q000201:enzymology; D045566:DNA, Cruciform; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D045585:Flap Endonucleases; D015966:Gene Expression Regulation, Fungal; D008540:Meiosis; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D049471:Pachytene Stage; D011401:Promoter Regions, Genetic / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D004720:Endonucleases; D045585:Flap Endonucleases; C411624:MUS81 protein, S cerevisiae; C112337:MMS4 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases