Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain.
Departamento de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain.
Nat Commun. 2016 Oct 31;7:13298. doi: 10.1038/ncomms13298.
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.
减数分裂重组产生同源染色体之间的交叉，这对于基因组单倍体化是必不可少的。联会复合体是一种“拉链”样的蛋白质组装体，将同源对连接在一起，并为将重组位点加工成交叉提供结构框架。人类在基因组中产生的交叉数量存在个体差异。最近，在 C14ORF39/SIX6OS1 中发现了一个匿名的基因变异，它影响人类的重组率。在这里，我们表明 C14ORF39/SIX6OS1 编码联会复合体中心元件的一个组成部分。酵母双杂交分析显示，SIX6OS1 与已确立的联会复合体中心元件 1 (SYCE1) 相互作用。缺乏 SIX6OS1 的小鼠在减数分裂前期的染色体联会中存在缺陷，这会导致在类似于粗线期的阶段停滞，并导致不育。与作为人类重组率调节剂的作用一致，SIX6OS1 对于在交叉形成之前适当处理中间重组结节是必不可少的。
