title: The Rad1-Rad10 nuclease promotes chromosome translocations between dispersed repeats.
abstract: Holliday junctions can be formed during homology-dependent repair of DNA double-strand breaks, and their resolution is essential for chromosome segregation and generation of crossover products. The Mus81-Mms4 and Yen1 nucleases are required for mitotic crossovers between chromosome homologs in Saccharomyces cerevisiae; however, crossovers between dispersed repeats are still detected in their absence. Here we show that the Rad1-Rad10 nuclease promotes formation of crossover and noncrossover recombinants between ectopic sequences. Crossover products were not recovered from the mus81Δ rad1Δ yen1Δ triple mutant, indicating that all three nucleases participate in processing recombination intermediates that form between dispersed repeats. We suggest a new mechanism for crossovers that involves Rad1-Rad10 clipping and resolution of a single Holliday junction-containing intermediate by Mus81-Mms4 or Yen1 cleavage or by replication. Consistent with the model, we show accumulation of Rad1-dependent joint molecules in the mus81Δ yen1Δ mutant.
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Mazón
authors.forename: Alicia F
authors.initials: AF
authors.lastname: Lam
authors.forename: Chu Kwen
authors.initials: CK
authors.lastname: Ho
authors.forename: Martin
authors.initials: M
authors.lastname: Kupiec
authors.forename: Lorraine S
authors.initials: LS
authors.lastname: Symington
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D045565:Holliday Junction Resolvases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D004720:Endonucleases; C411624:MUS81 protein, S cerevisiae; C069266:RAD1 protein, S cerevisiae; D045565:Holliday Junction Resolvases; C533749:Yen1 protein, S cerevisiae; C064162:RAD10 protein, S cerevisiae; D015719:Single-Strand Specific DNA and RNA Endonucleases; D045643:DNA Repair Enzymes