Current Biology
Volume 30, Issue 21, 2 November 2020, Pages 4113-4127.e6
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Article
COMET Functions as a PCH2 Cofactor in Regulating the HORMA Domain Protein ASY1

https://doi.org/10.1016/j.cub.2020.07.089Get rights and content
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Highlights

  • COMET is required for full chromosome synapsis, but not for DNA double-strand breaks

  • COMET serves as an adaptor protein for PCH2

  • COMET-PCH2 remove the HORMA protein ASY1 from the chromosome axis

  • COMET-PCH2 represent a conserved regulatory module of HORMA domain proteins

Summary

The formation of the chromosome axis is key to meiotic recombination and hence the correct distribution of chromosomes to meiotic products. A key component of the axis in Arabidopsis is the HORMA domain protein (HORMAD) ASY1, the homolog of Hop1 in yeast and HORMAD1/2 in mammals. The chromosomal association of ASY1 is dynamic, i.e., ASY1 is recruited to the axis at early prophase and later largely removed when homologous chromosomes synapse. PCH2/TRIP13 proteins are well-known regulators of meiotic HORMADs and required for their depletion from synapsed chromosomes. However, no direct interaction has been found between PCH2/TRIP13 and the presumptive HORMAD substrates in any organism other than in budding yeast. Thus, it remains largely elusive how the dynamics of ASY1 and other meiotic HORMADs are controlled. Here, we have identified COMET, the Arabidopsis homolog of human p31comet, which is known for its function in the spindle assembly checkpoint (SAC), as a central regulator of ASY1 dynamics in meiosis. We provide evidence that COMET controls ASY1 localization by serving as an adaptor for PCH2. Because ASY1 accumulates in the cytoplasm in early prophase and is persistently present on chromosomes in comet, we conclude that COMET is required for both the recruitment of ASY1 to the nucleus and the subsequent removal from the axis. The here-revealed function of COMET as an adaptor for PCH2 remarkably resembles the regulation of another HORMAD, Mad2, in the SAC in yeast and animals, revealing a conserved regulatory module of HORMA-domain-containing protein complexes.

Keywords

HORMA domain proteins
chromosome axis
COMET/p31comet
PCH2
ASY1
spindle assembly checkpoint
SAC

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