title: HORMAD1-dependent checkpoint/surveillance mechanism eliminates asynaptic oocytes.
abstract: Meiotic pachytene checkpoints monitor the failure of homologous recombination and synapsis to ensure faithful chromosome segregation during gamete formation. To date, the molecular basis of the mammalian pachytene checkpoints has remained largely unknown. We here report that mouse HORMAD1 is required for a meiotic prophase checkpoint that eliminates asynaptic oocytes. Hormad1-deficient mice are infertile and show an extensive failure of homologous pairing and synapsis, consistent with the evolutionarily conserved function of meiotic HORMA domain proteins. Unexpectedly, Hormad1-deficient ovaries contain a normal number of oocytes despite asynapsis and consequently produce aneuploid oocytes, indicating a checkpoint failure. By the analysis of Hormad1/Spo11 double mutants, the Hormad1 deficiency was found to abrogate the massive oocyte loss in the Spo11-deficient ovary. The Hormad1 deficiency also causes the eventual loss of pseudo sex body in the Spo11-deficient ovary and testis. These results suggest the involvement of HORMAD1 in the repressive chromatin domain formation that is proposed to be important in the meiotic prophase checkpoints. We also show the extensive phosphorylation of HORMAD1 in the Spo11-deficient testis and ovary, suggesting an involvement of novel DNA damage-independent phosphorylation signaling in the surveillance mechanism. Our present results provide clues to HORMAD1-dependent checkpoint in response to asynapsis in mammalian meiosis.
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogo
authors.forename: Makiko
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Tamae
authors.initials: T
authors.lastname: Ohye
authors.forename: Hidehito
authors.initials: H
authors.lastname: Inagaki
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D023902:Chromosome Pairing; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D018816:Genes, cdc; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D018797:Cell Cycle Proteins; D004706:Endodeoxyribonucleases; D000099257:Meiotic Recombination Protein SPO11; C506693:Nohma protein, mouse