Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1.
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.
Niu
Hengyao
H
Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5215, USA.
Wan
Lihong
L
Baumgartner
Bridget
B
Schaefer
Dana
D
Loidl
Josef
J
Hollingsworth
Nancy M
NM
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
D004268:DNA-Binding Proteins; C086672:HOP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D048369:MAP Kinase Kinase 1