title: Three distinct modes of Mec1/ATR and Tel1/ATM activation illustrate differential checkpoint targeting during budding yeast early meiosis.
abstract: Recombination and synapsis of homologous chromosomes are hallmarks of meiosis in many organisms. Meiotic recombination is initiated by Spo11-induced DNA double-strand breaks (DSBs), whereas chromosome synapsis is mediated by a tripartite structure named the synaptonemal complex (SC). Previously, we proposed that budding yeast SC is assembled via noncovalent interactions between the axial SC protein Red1, SUMO chains or conjugates, and the central SC protein Zip1. Incomplete synapsis and unrepaired DNA are monitored by Mec1/Tel1-dependent checkpoint responses that prevent exit from the pachytene stage. Here, our results distinguished three distinct modes of Mec1/Tec1 activation during early meiosis that led to phosphorylation of three targets, histone H2A at S129 (γH2A), Hop1, and Zip1, which are involved, respectively, in DNA replication, the interhomolog recombination and chromosome synapsis checkpoint, and destabilization of homology-independent centromere pairing. γH2A phosphorylation is Red1 independent and occurs prior to Spo11-induced DSBs. DSB- and Red1-dependent Hop1 phosphorylation is activated via interaction of the Red1-SUMO chain/conjugate ensemble with the Ddc1-Rad17-Mec3 (9-1-1) checkpoint complex and the Mre11-Rad50-Xrs2 complex. During SC assembly, Zip1 outcompetes 9-1-1 from the Red1-SUMO chain ensemble to attenuate Hop1 phosphorylation. In contrast, chromosome synapsis cannot attenuate DSB-dependent and Red1-independent Zip1 phosphorylation. These results reveal how DNA replication, DSB repair, and chromosome synapsis are differentially monitored by the meiotic checkpoint network.
authors.affiliation: Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yun-Hsin
authors.initials: YH
authors.lastname: Cheng
authors.forename: Chi-Ning
authors.initials: CN
authors.lastname: Chuang
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Shen
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Lin
authors.forename: Ting-Fang
authors.initials: TF
authors.lastname: Wang
mesh_terms: D023902:Chromosome Pairing; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C086672:HOP1 protein, S cerevisiae; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C086673:RED1 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C090118:Zip1 protein, S cerevisiae; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae