title: Smc5/6-Mms21 prevents and eliminates inappropriate recombination intermediates in meiosis.
abstract: Repairing broken chromosomes via joint molecule (JM) intermediates is hazardous and therefore strictly controlled in most organisms. Also in budding yeast meiosis, where production of enough crossovers via JMs is imperative, only a subset of DNA breaks are repaired via JMs, closely regulated by the ZMM pathway. The other breaks are repaired to non-crossovers, avoiding JM formation, through pathways that require the BLM/Sgs1 helicase. "Rogue" JMs that escape the ZMM pathway and BLM/Sgs1 are eliminated before metaphase by resolvases like Mus81-Mms4 to prevent chromosome nondisjunction. Here, we report the requirement of Smc5/6-Mms21 for antagonizing rogue JMs via two mechanisms; destabilizing early intermediates and resolving JMs. Elimination of the Mms21 SUMO E3-ligase domain leads to transient JM accumulation, depending on Mus81-Mms4 for resolution. Absence of Smc6 leads to persistent rogue JMs accumulation, preventing chromatin separation. We propose that the Smc5/6-Mms21 complex antagonizes toxic JMs by coordinating helicases and resolvases at D-Loops and HJs, respectively.
authors.affiliation: Max Perutz Laboratories, Chromosome Biology, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Xaver
authors.affiliation: Max Perutz Laboratories, Chromosome Biology, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Huang
authors.affiliation: Max Perutz Laboratories, Chromosome Biology, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Chen
authors.affiliation: Max Perutz Laboratories, Chromosome Biology, University of Vienna, Vienna Biocenter, Vienna, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Klein
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D020090:Chromosome Segregation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics; D045566:DNA, Cruciform / Q000235:genetics*; D059765:Homologous Recombination / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D046912:Multiprotein Complexes / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics; D025842:SUMO-1 Protein / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D045566:DNA, Cruciform; C500948:Mms21 protein, S cerevisiae; D046912:Multiprotein Complexes; C486627:SMC5 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases