title: C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility.
abstract: Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a 'zipper'-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation.
authors: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain.
authors: Laura
authors: L
authors: Gómez-H
authors: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain.
authors: Natalia
authors: N
authors: Felipe-Medina
authors: Departamento de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain.|Transgenic Facility, Nucleus platform, Universidad de Salamanca, 37007 Salamanca, Spain.
authors: Manuel
authors: M
authors: Sánchez-Martín
authors: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: Owen R
authors: http://orcid.org/0000-0002-3806-5403
authors: OR
authors: Davies
authors: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain.
authors: Isabel
authors: I
authors: Ramos
authors: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain.
authors: Ignacio
authors: I
authors: García-Tuñón
authors: Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584CM Utrecht, The Netherlands.
authors: Dirk G
authors: DG
authors: de Rooij
authors: Institute of Physiological Chemistry, Medical Faculty of TU Dresden, Fiedlerstrasse 42, 01307 Dresden, Germany.
authors: Ihsan
authors: I
authors: Dereli
authors: Institute of Physiological Chemistry, Medical Faculty of TU Dresden, Fiedlerstrasse 42, 01307 Dresden, Germany.
authors: Attila
authors: A
authors: Tóth
authors: Departamento de Biología Celular y Molecular, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain.
authors: José Luis
authors: JL
authors: Barbero
authors: Department of Cell and Developmental Biology, Biocenter, University of Würzburg, D-97074 Würzburg, Germany.
authors: Ricardo
authors: R
authors: Benavente
authors: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain.|Departamento de Fisiología y Farmacología, Universidad de Salamanca, 37007 Salamanca, Spain.
authors: Elena
authors: E
authors: Llano
authors: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain.
authors: Alberto M
authors: http://orcid.org/0000-0001-9264-3721
authors: AM
authors: Pendas
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D023902:Chromosome Pairing; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins; D018274:Electroporation; D005260:Female; D005298:Fertility; D014644:Genetic Variation; D016678:Genome; D057809:HEK293 Cells; D006238:Haploidy; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D013573:Synaptonemal Complex / Q000378:metabolism*; D013737:Testis / Q000473:pathology; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: C000628309:4930447C04Rik protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C504910:SYCE1 protein, mouse; C489754:Sycp1 protein, mouse; C490062:Sycp3 protein, mouse