title: Essential and Checkpoint Functions of Budding Yeast ATM and ATR during Meiotic Prophase Are Facilitated by Differential Phosphorylation of a Meiotic Adaptor Protein, Hop1.
abstract: A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis.
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, London, NW7 1AA, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Penedos
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, London, NW7 1AA, United Kingdom.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Johnson
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, S10 2TN, United Kingdom.
authors.forename: Emily
authors.initials: E
authors.lastname: Strong
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, S10 2TN, United Kingdom.
authors.forename: Alastair S
authors.initials: AS
authors.lastname: Goldman
authors.affiliation: Genome Damage & Stability Centre, University of Sussex, Brighton, BN1 9RQ, United Kingdom.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: Carballo
authors.affiliation: North West Cancer Research Fund Institute, School of Medical Sciences, Bangor University, Bangor, LL57 2UW, United Kingdom.
authors.forename: Rita S
authors.initials: RS
authors.lastname: Cha
mesh_terms: D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008540:Meiosis; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013696:Temperature
chemical_list: D004268:DNA-Binding Proteins; C086672:HOP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine