A conserved filamentous assembly underlies the structure of the meiotic chromosome axis
- University of California, San Diego, United States
- Ludwig-Maximilians-Universität München, Germany
- Institute of Molecular Biology of Barcelona, Spain
- Wesleyan University, United States
Abstract
The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that 'axis core proteins' from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify 'closure motifs' in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core proteins form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture, and likely also plays conserved roles in meiotic chromosome axis assembly and recombination control.
Data availability
Primary diffraction data for M. musculus SYCP3 tetramer structures have been deposited with the SBGrid Data Bank (https://data.sbgrid.org) under dataset numbers 583 (P21 crystal form) and 584 (P1 form).Reduced diffraction data and refined structural models have been deposited with the Protein Data Bank (www.pdb.org) under accession numbers 6DD8 (P21 crystal form) and 6DD9 (P1 form)
Article and author information
Author details
Funding
National Institutes of Health (R01 GM104141)
- Alan M V West
- Scott C Rosenberg
- Madison K Lehmer
- Qiaozhen Ye
- Kevin D Corbett
Human Frontier Science Program (RGP0008/2015)
- Franz Herzog
- Kevin D Corbett
National Science Foundation (Graduate Research Fellowship)
- Sarah N Ur
Ludwig Institute for Cancer Research
- Kevin D Corbett
National Institutes of Health (R15 GM116109)
- Amy J MacQueen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, West et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A conserved filamentous assembly underlies the structure of the meiotic chromosome axis
eLife 8:e40372.
https://doi.org/10.7554/eLife.40372
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Meiotic crossover recombination is essential for both accurate chromosome segregation and the generation of new haplotypes for natural selection to act upon. This requirement is known as crossover assurance and is one example of crossover control. While the conserved role of the ATPase, PCH-2, during meiotic prophase has been enigmatic, a universal phenotype when pch-2 or its orthologs are mutated is a change in the number and distribution of meiotic crossovers. Here, we show that PCH-2 controls the number and distribution of crossovers by antagonizing their formation. This antagonism produces different effects at different stages of meiotic prophase: early in meiotic prophase, PCH-2 prevents double-strand breaks from becoming crossover-eligible intermediates, limiting crossover formation at sites of initial double-strand break formation and homolog interactions. Later in meiotic prophase, PCH-2 winnows the number of crossover-eligible intermediates, contributing to the designation of crossovers and ultimately, crossover assurance. We also demonstrate that PCH-2 accomplishes this regulation through the meiotic HORMAD, HIM-3. Our data strongly support a model in which PCH-2’s conserved role is to remodel meiotic HORMADs throughout meiotic prophase to destabilize crossover-eligible precursors and coordinate meiotic recombination with synapsis, ensuring the progressive implementation of meiotic recombination and explaining its function in the pachytene checkpoint and crossover control.
