title: A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility.
abstract: The synaptonemal complex (SC) is a proteinaceous, meiosis-specific structure that is highly conserved in evolution. During meiosis, the SC mediates synapsis of homologous chromosomes. It is essential for proper recombination and segregation of homologous chromosomes, and therefore for genome haploidization. Mutations in human SC genes can cause infertility. In order to gain a better understanding of the process of SC assembly in a model system that would be relevant for humans, we are investigating meiosis in mice. Here, we report on a newly identified component of the murine SC, which we named SYCE3. SYCE3 is strongly conserved among mammals and localizes to the central element (CE) of the SC. By generating a Syce3 knockout mouse, we found that SYCE3 is required for fertility in both sexes. Loss of SYCE3 blocks synapsis initiation and results in meiotic arrest. In the absence of SYCE3, initiation of meiotic recombination appears to be normal, but its progression is severely impaired resulting in complete absence of MLH1 foci, which are presumed markers of crossovers in wild-type meiocytes. In the process of SC assembly, SYCE3 is required downstream of transverse filament protein SYCP1, but upstream of the other previously described CE-specific proteins. We conclude that SYCE3 enables chromosome loading of the other CE-specific proteins, which in turn would promote synapsis between homologous chromosomes.
authors.affiliation: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schramm
authors.forename: Johanna
authors.initials: J
authors.lastname: Fraune
authors.forename: Ronald
authors.initials: R
authors.lastname: Naumann
authors.forename: Abrahan
authors.initials: A
authors.lastname: Hernandez-Hernandez
authors.forename: Christer
authors.initials: C
authors.lastname: Höög
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Cooke
authors.forename: Manfred
authors.initials: M
authors.lastname: Alsheimer
authors.forename: Ricardo
authors.initials: R
authors.lastname: Benavente
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins; D005260:Female; D005298:Fertility; D005838:Genotype; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D016415:Sequence Alignment; D013090:Spermatocytes / Q000378:metabolism; D013573:Synaptonemal Complex / Q000502:physiology*; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; C504910:SYCE1 protein, mouse; C504911:SYCE2 protein, mouse; C489754:Sycp1 protein, mouse; C515820:TEX12 protein, mouse; D000070957:MutL Protein Homolog 1