title: BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism.
abstract: The BLM helicase has been shown to maintain genome stability by preventing accumulation of aberrant recombination intermediates. We show here that the Saccharomyces cerevisiae BLM ortholog, Sgs1, plays an integral role in normal meiotic recombination, beyond its documented activity limiting aberrant recombination intermediates. In wild-type meiosis, temporally and mechanistically distinct pathways produce crossover and noncrossover recombinants. Crossovers form late in meiosis I prophase, by polo kinase-triggered resolution of Holliday junction (HJ) intermediates. Noncrossovers form earlier, via processes that do not involve stable HJ intermediates. In contrast, sgs1 mutants abolish early noncrossover formation. Instead, both noncrossovers and crossovers form by late HJ intermediate resolution, using an alternate pathway requiring the overlapping activities of Mus81-Mms4, Yen1, and Slx1-Slx4, nucleases with minor roles in wild-type meiosis. We conclude that Sgs1 is a primary regulator of recombination pathway choice during meiosis and suggest a similar function in the mitotic cell cycle.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Arnaud
authors.initials: A
authors.lastname: De Muyt
authors.forename: Lea
authors.initials: L
authors.lastname: Jessop
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kolar
authors.forename: Anuradha
authors.initials: A
authors.lastname: Sourirajan
authors.forename: Jianhong
authors.initials: J
authors.lastname: Chen
authors.forename: Yaron
authors.initials: Y
authors.lastname: Dayani
authors.forename: Michael
authors.initials: M
authors.lastname: Lichten
mesh_terms: D003434:Crossing Over, Genetic / Q000502:physiology*; D045566:DNA, Cruciform / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D045585:Flap Endonucleases / Q000235:genetics / Q000378:metabolism; D045565:Holliday Junction Resolvases / Q000235:genetics / Q000378:metabolism; D049469:Meiotic Prophase I / Q000502:physiology*; D009154:Mutation; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D045566:DNA, Cruciform; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D045585:Flap Endonucleases; C411624:MUS81 protein, S cerevisiae; C507304:SLX1 protein, S cerevisiae; C505436:SLX4 protein, S cerevisiae; D045565:Holliday Junction Resolvases; C533749:Yen1 protein, S cerevisiae; C112337:MMS4 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases