Mutation of the Mouse Syce1 Gene Disrupts Synapsis and Suggests a Link between Synaptonemal Complex Structural Components and DNA Repair

Abstract

In mammals, the synaptonemal complex is a structure required to complete crossover recombination. Although suggested by cytological work, in vivo links between the structural proteins of the synaptonemal complex and the proteins of the recombination process have not previously been made. The central element of the synaptonemal complex is traversed by DNA at sites of recombination and presents a logical place to look for interactions between these components. There are four known central element proteins, three of which have previously been mutated. Here, we complete the set by creating a null mutation in the Syce1 gene in mouse. The resulting disruption of synapsis in these animals has allowed us to demonstrate a biochemical interaction between the structural protein SYCE2 and the repair protein RAD51. In normal meiosis, this interaction may be responsible for promoting homologous synapsis from sites of recombination.

Author Summary

Production of sperm and eggs, also known as gametes, requires a reduction in the number of copies of the genome, from the two found in most cells of the body to the single copy found in gametes. This is a complex process, made even more complex because it is coupled with recombination, a process that is an important contributor to genetic diversity. Mammals and many other organisms achieve reduction and recombination through a process called meiosis, which is recognisable by the presence of a distinctive structure—the synaptonemal complex—that links the chromosomes together and is essential for meiosis to complete. We have made mice that lack SYCE1, a protein component of the synaptonemal complex. In these animals, meiosis is blocked at a particular stage, and this has allowed us to detect co-localisation and interactions—likely indirect—between enzymes involved in recombination and structural proteins involved in meiosis. This provides a starting point to understand in biochemical detail the protein links between structure and function in meiosis. Mutations or variants in the genes encoding such proteins are likely contributors to variations in fertility and to abnormalities in chromosome number.