title: Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1.
abstract: Meiotic recombination differs from mitotic recombination in that DSBs are repaired using homologous chromosomes, rather than sister chromatids. This change in partner choice is due in part to a barrier to sister chromatid repair (BSCR) created by the meiosis-specific kinase, Mek1, in a complex with two other meiosis-specific proteins, Hop1 and Red1. HOP1 contains two functional domains, called the N and C domains. Analysis of a point mutation that specifically inactivates the C domain (hop1-K593A) reveals that the N domain is sufficient for Hop1 localization to chromosomes and for Red1 and Hop1 interactions. The C domain is needed for spore viability, for chromosome synapsis, and for preventing DMC1-independent DSB repair, indicating it plays a role in the BSCR. All of the hop1-K593A phenotypes can be bypassed by fusion of ectopic dimerization domains to Mek1, suggesting that the function of the C domain is to promote Mek1 dimerization. Hop1 is a DSB-dependent phosphoprotein, whose phosphorylation requires the presence of the C domain, but is independent of MEK1. These results suggest a model in which Hop1 phosphorylation in response to DSBs triggers dimerization of Mek1 via the Hop1 C domain, thereby enabling Mek1 to phosphorylate target proteins that prevent repair of DSBs by sister chromatids.
authors.affiliation: Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5215, USA.
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.forename: Lihong
authors.initials: L
authors.lastname: Wan
authors.forename: Bridget
authors.initials: B
authors.lastname: Baumgartner
authors.forename: Dana
authors.initials: D
authors.lastname: Schaefer
authors.forename: Josef
authors.initials: J
authors.lastname: Loidl
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hollingsworth
mesh_terms: D002874:Chromosome Mapping; D015825:Chromosomes, Fungal; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005838:Genotype; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology*; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013172:Spores, Fungal / Q000502:physiology; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; C086672:HOP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D048369:MAP Kinase Kinase 1