Cell and Molecular Biology Monday Seminar Series: Owen Davies (Newcastle University) - Structural basis of meiotic chromosome synapsis through SYCP1 self-assembly

  • Title:  Structural basis of meiotic chromosome synapsis through SYCP1 self-assembly
  • When:  Monday 18 September 2017
  • Time: 12 pm
  • Location:  Daniel Rutherford Building, G.27, Lecture Theatre 1, King's Buildings
  • Speaker:  Owen Davies, Institute for Cell and Molecular Biosciences, Newcastle University
  • Host: JP Arulanandam

Summary

The process of reductive cell division by meiosis is essential for fertility and genetic diversity in all sexually reproducing organisms. At its centre is the synaptonemal complex (SC), a ‘zipper’-like protein assembly that binds together homologous chromosome pairs during prophase of the first meiotic division. The SC imposes a unique structure upon meiotic chromosomes and provides the essential three-dimensional framework for meiotic recombination and crossover formation. Indeed, structural integrity of the SC is essential for meiotic division and fertility, and errors in its formation are associated with infertility, recurrent miscarriage and aneuploidies such as Down’s syndrome.

In mammals, the principal SC component is SYCP1, a 976 amino acid protein that bridges between the midline central element and chromosome-bound lateral element, with its N- and C-termini located within each of these regions respectively. Here, we report the structure of SYCP1 and the molecular basis of its self-assembly through sites within its N- and C-terminal regions. Small-angle X-ray and multi-angle light scattering experiments reveal that SYCP1 adopts an obligate structure of a bifurcated elongated tetramer. The crystal structures of its N- and C-terminal self-assembly regions reveal two distinct mechanisms of assembly, through co-operativity at the N-terminus and through a pH sensor at the C-terminus. Taken together, our data lead to a full molecular model for the structure of SYCP1 and how its self-assembly underlies the cooperative and continuous synapsis achieved along the length of homologous chromosome pairs during meiosis.

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