title: mre11S--a yeast mutation that blocks double-strand-break processing and permits nonhomologous synapsis in meiosis.
abstract: During meiotic prophase the repair of self-inflicted DNA double-strand break (DSB) damage leads to meiotic recombination in yeast. We employed a genetic screen to specifically characterize cellular functions that become essential after this DSB formation. As a result a new allele of MRE11, termed mre11S (for Separation of functions) was isolated that allows initiation but not processing and repair of meiotic DSBs similar to the well-characterized rad50S allele. In contrast, the mre11-1 allele blocks initiation of meiotic DSBs as reported previously by others. The mre11S allele, which is mutated in the 5' part of the gene, can partially complement mre11 alleles disrupted close to the 3' end that cannot initiate DSBs when homozygous. This suggests homodimerization of the Mre11 protein and the presence of separate domains for DSB initiation and 5' resection. The fact that two genes, RAD50 and MRE11, required for DSB processing are also essential for DSB initiation dictates a model in which a bifunctional initiation/repair complex is required to initiate meiotic recombination. A subset of mre11S nuclei was shown to perform extensive but partially nonhomologous synapsis. We propose that the unprocessed DSBs present in mre11S allow for synapsis, but that homologous synapsis is only ensured at a later stage of recombination.
authors.affiliation: Institut für Botanik, Abteilung für Zytologie und Genetik, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Nairz
authors.forename: F
authors.initials: F
authors.lastname: Klein
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004271:DNA, Fungal / Q000378:metabolism; D019281:Dimerization; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D017404:In Situ Hybridization, Fluorescence; D008540:Meiosis / Q000235:genetics*; D008854:Microscopy, Electron; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013573:Synaptonemal Complex / Q000235:genetics
chemical_list: D017931:DNA Primers; D004271:DNA, Fungal; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae