Current Biology
Volume 30, Issue 22, 16 November 2020, Pages 4413-4424.e5
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Article
Homeostatic Control of Meiotic Prophase Checkpoint Function by Pch2 and Hop1

https://doi.org/10.1016/j.cub.2020.08.064Get rights and content
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Highlights

  • Feedback regulation between Hop1, Zip1, and Pch2 influences the synaptonemal complex

  • Pch2 and Hop1 collaborate to mediate general meiotic prophase checkpoint function

  • Pch2 has activating and silencing roles in meiotic prophase checkpoint function

  • Synaptonemal complex polymerization dictates switch-like behavior of Pch2 function

Summary

Checkpoint cascades link cell cycle progression with essential chromosomal processes. During meiotic prophase, recombination and chromosome synapsis are monitored by what are considered distinct checkpoints. In budding yeast, cells that lack the AAA+ ATPase Pch2 show an impaired cell cycle arrest in response to synapsis defects. However, unperturbed pch2Δ cells are delayed in meiotic prophase, suggesting paradoxical roles for Pch2 in cell cycle progression. Here, we provide insight into the checkpoint roles of Pch2 and its connection to Hop1, a HORMA domain-containing client protein. Contrary to current understanding, we find that Pch2 (together with Hop1) is crucial for checkpoint function in response to both recombination and synapsis defects, thus revealing a shared meiotic checkpoint cascade. Meiotic checkpoint responses are transduced by DNA break-dependent phosphorylation of Hop1. Based on our data and on the described effect of Pch2 on HORMA topology, we propose that Pch2 promotes checkpoint proficiency by catalyzing the availability of signaling-competent Hop1. Conversely, we demonstrate that Pch2 can act as a checkpoint silencer, also in the face of persistent DNA repair defects. We establish a framework in which Pch2 and Hop1 form a homeostatic module that governs general meiotic checkpoint function. We show that this module can—depending on the cellular context—fuel or extinguish meiotic checkpoint function, which explains the contradictory roles of Pch2 in cell cycle control. Within the meiotic prophase checkpoint, the Pch2-Hop1 module thus operates analogous to the Pch2/TRIP13-Mad2 module in the spindle assembly checkpoint that monitors chromosome segregation.

Keywords

meiosis
checkpoint
AAA+ ATPase
HORMA domain
recombination
synapsis
DNA repair

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