title: High copy number suppression of the meiotic arrest caused by a dmc1 mutation: REC114 imposes an early recombination block and RAD54 promotes a DMC1-independent DSB repair pathway.
abstract: BACKGROUND
  DMC1, the meiosis-specific eukaryotic homologue of bacterial recA, is required for completion of meiotic recombination and cell cycle progression past prophase. In a dmc1 mutant, double strand break recombination intermediates accumulate and cells arrest in prophase. We isolated genes which, when present at high copy numbers, suppress the meiotic arrest phenotype conferred by dmc1 mutations.
  
  
  RESULTS
  Among the genes isolated were two which suppress arrest by altering the recombination process. REC114 suppresses formation of double strand break (DSB) recombination intermediates. The low viability of spores produced by dmc1 mutants carrying high copy numbers of REC114 is rescued when reductional segregation is bypassed by mutation of spo13. High copy numbers of RAD54 suppress dmc1 arrest, promote DSB repair, and allow formation of viable spores following reductional segregation. Analysis of the combined effects of a null mutation in RED1, a gene required for meiotic chromosome structure, with null mutations in RAD54 and DMC1 shows that RAD54, while not normally important for repair of DSBs during meiosis, is required for efficient repair of breaks by the intersister recombination pathway that operates in red1 dmc1 double mutants.
  
  
  CONCLUSIONS
  Over-expression of REC114 suppresses meiotic arrest by preventing formation of DSBs. High copy numbers of RAD54 activate a DMC1-independent mechanism that promotes repair of DSBs by homology-mediated recombination. The ability of RAD54 to promote DMC1-independent recombination is proposed to involve suppression of a constraint that normally promotes recombination between homologous chromatids rather than sisters.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago IL 60637, USA. dbishop@midway.uchicago.edu
authors.forename: D K
authors.initials: DK
authors.lastname: Bishop
authors.forename: Y
authors.initials: Y
authors.lastname: Nikolski
authors.forename: J
authors.initials: J
authors.lastname: Oshiro
authors.forename: J
authors.initials: J
authors.lastname: Chon
authors.forename: M
authors.initials: M
authors.lastname: Shinohara
authors.forename: X
authors.initials: X
authors.lastname: Chen
mesh_terms: D018797:Cell Cycle Proteins; D004265:DNA Helicases; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D015723:Gene Library; D008540:Meiosis; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D045522:Recombinases; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; C513033:DMC1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C080622:REC114 protein, S cerevisiae; C086673:RED1 protein, S cerevisiae; D011994:Recombinant Proteins; D045522:Recombinases; C097192:SPO13 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes