title: Mek1 stabilizes Hop1-Thr318 phosphorylation to promote interhomolog recombination and checkpoint responses during yeast meiosis.
abstract: Red1, Hop1 and Mek1 are three yeast meiosis-specific chromosomal proteins that uphold the interhomolog (IH) bias of meiotic recombination. Mek1 is also an effector protein kinase in a checkpoint that responds to aberrant DNA and/or axis structure. The activation of Mek1 requires Red1-dependent Hop1-Thr(T)318 phosphorylation, which is mediated by Mec1 and Tel1, the yeast homologs of the mammalian DNA damage sensor kinases ATR and ATM. As the ectopic expression of Mek1-glutathione S-transferase (GST) was shown to promote IH recombination in the absence of Mec1/Tel1-dependent checkpoint function, it was proposed that Mek1 might play dual roles during meiosis by directly phosphorylating targets that are involved in the recombination checkpoint. Here, we report that Mek1 has a positive feedback activity in the stabilization of Mec1/Tel1-mediated Hop1-T318 phosphorylation against the dephosphorylation mediated by protein phosphatase 4. Our results also reveal that GST-Mek1 or Mek1-GST further increases Hop1-T318 phosphorylation. This positive feedback function of Mek1 is independent of Mek1's kinase activity, but dependent on Mek1's forkhead-associated (FHA) domain and its arginine 51 residue. Arginine 51 directly mediates the interaction of Mek1-FHA and phosphorylated Hop1-T318. We suggest that the Hop1-Mek1 interaction is similar to the Rad53-Dun1 signaling pathway, which is mediated through the interaction of phosphorylated Rad53 and Dun1-FHA.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chi-Ning
authors.initials: CN
authors.lastname: Chuang
authors.forename: Yun-Hsin
authors.initials: YH
authors.lastname: Cheng
authors.forename: Ting-Fang
authors.initials: TF
authors.lastname: Wang
mesh_terms: D045163:Antibodies, Phospho-Specific; D001120:Arginine / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019281:Dimerization; D017353:Gene Deletion; D008540:Meiosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism
chemical_list: D045163:Antibodies, Phospho-Specific; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C086672:HOP1 protein, S cerevisiae; D009687:Nuclear Proteins; C528119:Pch2 protein, S cerevisiae; C501395:RAD17 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C090118:Zip1 protein, S cerevisiae; D013912:Threonine; D001120:Arginine; D017346:Protein Serine-Threonine Kinases; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes