C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility

Laura Gómez-H, Natalia Felipe-Medina, Manuel Sánchez-Martín, Owen R. Davies, Isabel Ramos, Ignacio García-Tuñón, Dirk G. de Rooij, Ihsan Dereli, Attila Tóth, José Luis Barbero, Ricardo Benavente, Elena Llano () and Alberto M. Pendas ()
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Laura Gómez-H: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca)
Natalia Felipe-Medina: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca)
Manuel Sánchez-Martín: Universidad de Salamanca
Owen R. Davies: Institute for Cell and Molecular Biosciences, Newcastle University
Isabel Ramos: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca)
Ignacio García-Tuñón: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca)
Dirk G. de Rooij: Reproductive Biology Group, Faculty of Science, Utrecht University
Ihsan Dereli: Institute of Physiological Chemistry, Medical Faculty of TU Dresden
Attila Tóth: Institute of Physiological Chemistry, Medical Faculty of TU Dresden
José Luis Barbero: Centro de Investigaciones Biológicas (CSIC)
Ricardo Benavente: Biocenter, University of Würzburg
Elena Llano: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca)
Alberto M. Pendas: Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca)

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13298

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