title: Phosphorylation of the Synaptonemal Complex Protein Zip1 Regulates the Crossover/Noncrossover Decision during Yeast Meiosis.
abstract: Interhomolog crossovers promote proper chromosome segregation during meiosis and are formed by the regulated repair of programmed double-strand breaks. This regulation requires components of the synaptonemal complex (SC), a proteinaceous structure formed between homologous chromosomes. In yeast, SC formation requires the "ZMM" genes, which encode a functionally diverse set of proteins, including the transverse filament protein, Zip1. In wild-type meiosis, Zmm proteins promote the biased resolution of recombination intermediates into crossovers that are distributed throughout the genome by interference. In contrast, noncrossovers are formed primarily through synthesis-dependent strand annealing mediated by the Sgs1 helicase. This work identifies a conserved region on the C terminus of Zip1 (called Zip1 4S), whose phosphorylation is required for the ZMM pathway of crossover formation. Zip1 4S phosphorylation is promoted both by double-strand breaks (DSBs) and the meiosis-specific kinase, MEK1/MRE4, demonstrating a role for MEK1 in the regulation of interhomolog crossover formation, as well as interhomolog bias. Failure to phosphorylate Zip1 4S results in meiotic prophase arrest, specifically in the absence of SGS1. This gain of function meiotic arrest phenotype is suppressed by spo11Δ, suggesting that it is due to unrepaired breaks triggering the meiotic recombination checkpoint. Epistasis experiments combining deletions of individual ZMM genes with sgs1-md zip1-4A indicate that Zip1 4S phosphorylation functions prior to the other ZMMs. These results suggest that phosphorylation of Zip1 at DSBs commits those breaks to repair via the ZMM pathway and provides a mechanism by which the crossover/noncrossover decision can be dynamically regulated during yeast meiosis.
authors.affiliation: Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Ray T
authors.initials: RT
authors.lastname: Suhandynata
authors.affiliation: Center for Gene Regulation in Health and Disease and Department of Biological Sciences, Cleveland State University, Cleveland, Ohio, United States of America.
authors.forename: Rima
authors.initials: R
authors.lastname: Sandhu
authors.affiliation: Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Beth
authors.initials: B
authors.lastname: Rockmill
authors.affiliation: Molecular Biology Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York City, New York, United States of America.|Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York City, New York, United States of America.
authors.forename: Neeman
authors.initials: N
authors.lastname: Mohibullah
authors.affiliation: Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, United States of America.
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California, United States of America.|Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Liang
authors.affiliation: Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Lo
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.|Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Danny E
authors.initials: DE
authors.lastname: Miller
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California, United States of America.|Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Center for Gene Regulation in Health and Disease and Department of Biological Sciences, Cleveland State University, Cleveland, Ohio, United States of America.
authors.forename: G Valentin
authors.initials: GV
authors.lastname: Börner
authors.affiliation: Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hollingsworth
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017124:Conserved Sequence; D003434:Crossing Over, Genetic; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D008540:Meiosis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013573:Synaptonemal Complex / Q000378:metabolism*; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D004706:Endodeoxyribonucleases; D050505:Mutant Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D053484:RecQ Helicases; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C090118:Zip1 protein, S cerevisiae; C518938:Spo11 protein, S cerevisiae; D000099257:Meiotic Recombination Protein SPO11; C090472:SGS1 protein, S cerevisiae