SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis

Author:

Billmyre Katherine Kretovich1ORCID,Kesler Emily A.1,Tsuchiya Dai1ORCID,Corbin Timothy J.1ORCID,Weaver Kyle1ORCID,Moran Andrea1,Yu Zulin1ORCID,Adams Lane1ORCID,Delventhal Kym1ORCID,Durnin Michael1,Davies Owen Richard2ORCID,Hawley R. Scott13ORCID

Affiliation:

1. Stowers Institute for Medical Research, Kansas City, MO 64110, USA.

2. Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.

3. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Abstract

In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure, the synaptonemal complex (SC). While the SC’s overall structure is highly conserved across eukaryotes, its constituent proteins diverge between phyla. Transverse filament protein, SYCP1, spans the width of the SC and undergoes amino-terminal head-to-head self-assembly in vitro through a motif that is unusually highly conserved across kingdoms of life. Here, we report creation of mouse mutants, Sycp1 L102E and Sycp1 L106E , that target SYCP1’s head-to-head interface. L106E resulted in a complete loss of synapsis, while L102E had no apparent effect on synapsis, in agreement with their differential effects on the SYCP1 head-to-head interface in molecular dynamics simulations. In Sycp1 L106E mice, homologs aligned and recruited low levels of mutant SYCP1 and other SC proteins, but the absence of synapsis led to failure of crossover formation and meiotic arrest. We conclude that SYCP1’s conserved head-to-head interface is essential for meiotic chromosome synapsis in vivo.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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