title: Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis.
abstract: Meiotic recombination and chromosome synapsis between homologous chromosomes are essential for proper chromosome segregation at the first meiotic division. While recombination and synapsis, as well as checkpoints that monitor these two events, take place in the context of a prophase I-specific axial chromosome structure, it remains unclear how chromosome axis components contribute to these processes. We show here that many protein components of the meiotic chromosome axis, including SYCP2, SYCP3, HORMAD1, HORMAD2, SMC3, STAG3, and REC8, become post-translationally modified by phosphorylation during the prophase I stage. We found that HORMAD1 and SMC3 are phosphorylated at a consensus site for the ATM/ATR checkpoint kinase and that the phosphorylated forms of HORMAD1 and SMC3 localize preferentially to unsynapsed chromosomal regions where synapsis has not yet occurred, but not to synapsed or desynapsed regions. We investigated the genetic requirements for the phosphorylation events and revealed that the phosphorylation levels of HORMAD1, HORMAD2, and SMC3 are dramatically reduced in the absence of initiation of meiotic recombination, whereas BRCA1 and SYCP3 are required for normal levels of phosphorylation of HORMAD1 and HORMAD2, but not of SMC3. Interestingly, reduced HORMAD1 and HORMAD2 phosphorylation is associated with impaired targeting of the MSUC (meiotic silencing of unsynapsed chromatin) machinery to unsynapsed chromosomes, suggesting that these post-translational events contribute to the regulation of the synapsis surveillance system. We propose that modifications of chromosome axis components serve as signals that facilitate chromosomal events including recombination, checkpoint control, transcription, and synapsis regulation.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. tomoyuki.fukuda@ki.se
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fukuda
authors.forename: Florencia
authors.initials: F
authors.lastname: Pratto
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
authors.forename: James M A
authors.initials: JM
authors.lastname: Turner
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Camerini-Otero
authors.forename: Christer
authors.initials: C
authors.lastname: Höög
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics*; D004268:DNA-Binding Proteins; D008297:Male; D008540:Meiosis / Q000235:genetics*; D049469:Meiotic Prophase I / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000235:genetics; D011995:Recombination, Genetic; D013090:Spermatocytes / Q000378:metabolism; D013573:Synaptonemal Complex
chemical_list: D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C492317:SMC3 protein, mouse; C546539:HORMAD2 protein, mouse; C506693:Nohma protein, mouse; C465863:Rec8 protein, mouse; C498637:Stag3 protein, mouse; C498354:Sycp2 protein, mouse; C490062:Sycp3 protein, mouse