Structural maturation of SYCP1-mediated meiotic chromosome synapsis by SYCE3
Davies Lab paper featured in Nature Structural and Molecular Biology.
Authors
Crichton, J.H., Dunce, J.M., Dunne, O.M., Salmon, L.J., Devenney, P.S., Lawson, J., Adams, I.R. and Davies, O.R.
Summary of Paper by Lori Koch
The process of swapping pieces of DNA between chromosomes, recombination, must occur during the specialised cell division that creates egg and sperm for reproduction. In order to recombine their DNA, ‘matching’ (homologous) chromosomes are physically bridged by the synaptonemal complex. The complex appears similar to a zipper in electron micrographs but how the proteins actually work together in the cell, so that the complex can hold chromosomes but allow for DNA movement, is unclear. In their study recently published in Nature Structural and Molecular Biology, scientists in the Davies and Adams (HGU, University of Edinburgh) groups led by Dr. James Crichton and Dr. James Dunce identified how the central element protein SYCE3 is required for the formation of a normal synaptonemal complex in cells by acting as a kind of adapter between different ‘building block’ protein complexes. Initially they identified that SYCE3 interacts with the major lattice protein of the complex SYCP1 by yeast-two-hybrid assay as well as in vitro pulldowns. The interaction between SYCP1 and SYCE3 was quite strong, with nanomolar affinity determined by ITC. SYCP1 forms tetramer (4 copies of SYCP1) complexes on its own but when SYCE3 was added they observed a 2:1 SYCP1-SYCE3 hetero-trimer by SEC-MALS. Based on their structural assays, they hypothesized that an interface required for SYCE3 self-assembly may be important for overall complex structure. They generated CRISPR-Cas9 modified mice in which SYCE3 was either deleted or carrying point mutations which disrupt SYCE3 self-assembly but not SYCE3-SYCP1 binding. Analysis of these animals revealed that the SYCE3 self-assembly interface mutant created worse defects in complex structure than animals missing SYCE3 entirely (∆/∆). Overall their data supports a model in which SYCE3 is a lynchpin in the assembly of the lattice-like but also dynamic synaptonemal complex.