1. Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis.
- Author
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Fukuda T, Pratto F, Schimenti JC, Turner JM, Camerini-Otero RD, and Höög C
- Subjects
- Animals, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Chondroitin Sulfate Proteoglycans genetics, Chondroitin Sulfate Proteoglycans metabolism, Chromatin genetics, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, DNA-Binding Proteins, Male, Meiotic Prophase I genetics, Mice, Mice, Inbred C57BL, Nuclear Proteins genetics, Nuclear Proteins metabolism, Phosphoproteins genetics, Phosphoproteins metabolism, Protein Processing, Post-Translational genetics, Spermatocytes metabolism, Synaptonemal Complex, Chromosome Pairing genetics, Chromosome Segregation genetics, Chromosomes genetics, Meiosis genetics, Phosphorylation, Recombination, Genetic
- 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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2012
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