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Structural basis of meiotic chromosome synapsis through SYCP1 self-assembly

DOI: 10.1038/s41594-018-0078-9 DOI Help

Authors: James M. Dunce (Newcastle University) , Orla M. Dunne (Newcastle University) , Matthew Ratcliff (Newcastle University) , Claudia Millán (Institute of Molecular Biology of Barcelona (IBMB-CSIC)) , Suzanne Madgwick (Newcastle University) , Isabel Uson (Institute of Molecular Biology of Barcelona (IBMB-CSIC)) , Owen R. Davies (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 7

State: Published (Approved)
Published: June 2018
Diamond Proposal Number(s): 9948 , 13587 , 14435 , 15580 , 15897

Open Access Open Access

Abstract: Meiotic chromosomes adopt unique structures in which linear arrays of chromatin loops are bound together in homologous chromosome pairs by a supramolecular protein assembly, the synaptonemal complex. This three-dimensional scaffold provides the essential structural framework for genetic exchange by crossing over and subsequent homolog segregation. The core architecture of the synaptonemal complex is provided by SYCP1. Here we report the structure and self-assembly mechanism of human SYCP1 through X-ray crystallographic and biophysical studies. SYCP1 has an obligate tetrameric structure in which an N-terminal four-helical bundle bifurcates into two elongated C-terminal dimeric coiled-coils. This building block assembles into a zipper-like lattice through two self-assembly sites. N-terminal sites undergo cooperative head-to-head assembly in the midline, while C-terminal sites interact back to back on the chromosome axis. Our work reveals the underlying molecular structure of the synaptonemal complex in which SYCP1 self-assembly generates a supramolecular lattice that mediates meiotic chromosome synapsis.

Journal Keywords: Chromosomes; DNA recombination; SAXS; Supramolecular assembly; X-ray crystallography

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS , I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Documents:
s41594-018-0078-9.pdf