PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.

The conserved ATPase, PCH-2/TRIP13, is required during both the spindle checkpoint and meiotic prophase. However, its specific role in regulating meiotic homolog pairing, synapsis and recombination has been enigmatic. Here, we report that this enzyme is required to proofread meiotic homolog interact...

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Main Authors: Stefani Giacopazzi, Daniel Vong, Alice Devigne, Needhi Bhalla
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-07-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1008904
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author Stefani Giacopazzi
Daniel Vong
Alice Devigne
Needhi Bhalla
author_facet Stefani Giacopazzi
Daniel Vong
Alice Devigne
Needhi Bhalla
author_sort Stefani Giacopazzi
collection DOAJ
description The conserved ATPase, PCH-2/TRIP13, is required during both the spindle checkpoint and meiotic prophase. However, its specific role in regulating meiotic homolog pairing, synapsis and recombination has been enigmatic. Here, we report that this enzyme is required to proofread meiotic homolog interactions. We generated a mutant version of PCH-2 in C. elegans that binds ATP but cannot hydrolyze it: pch-2E253Q. In vitro, this mutant can bind a known substrate but is unable to remodel it. This mutation results in some non-homologous synapsis and impaired crossover assurance. Surprisingly, worms with a null mutation in PCH-2's adapter protein, CMT-1, the ortholog of p31comet, localize PCH-2 to meiotic chromosomes, exhibit non-homologous synapsis and lose crossover assurance. The similarity in phenotypes between cmt-1 and pch-2E253Q mutants suggest that PCH-2 can bind its meiotic substrates in the absence of CMT-1, in contrast to its role during the spindle checkpoint, but requires its adapter to hydrolyze ATP and remodel them.
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spelling doaj.art-8cab01d7e64c4da8aa29b25433269e7c2022-12-21T22:00:33ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042020-07-01167e100890410.1371/journal.pgen.1008904PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.Stefani GiacopazziDaniel VongAlice DevigneNeedhi BhallaThe conserved ATPase, PCH-2/TRIP13, is required during both the spindle checkpoint and meiotic prophase. However, its specific role in regulating meiotic homolog pairing, synapsis and recombination has been enigmatic. Here, we report that this enzyme is required to proofread meiotic homolog interactions. We generated a mutant version of PCH-2 in C. elegans that binds ATP but cannot hydrolyze it: pch-2E253Q. In vitro, this mutant can bind a known substrate but is unable to remodel it. This mutation results in some non-homologous synapsis and impaired crossover assurance. Surprisingly, worms with a null mutation in PCH-2's adapter protein, CMT-1, the ortholog of p31comet, localize PCH-2 to meiotic chromosomes, exhibit non-homologous synapsis and lose crossover assurance. The similarity in phenotypes between cmt-1 and pch-2E253Q mutants suggest that PCH-2 can bind its meiotic substrates in the absence of CMT-1, in contrast to its role during the spindle checkpoint, but requires its adapter to hydrolyze ATP and remodel them.https://doi.org/10.1371/journal.pgen.1008904
spellingShingle Stefani Giacopazzi
Daniel Vong
Alice Devigne
Needhi Bhalla
PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.
PLoS Genetics
title PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.
title_full PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.
title_fullStr PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.
title_full_unstemmed PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.
title_short PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions.
title_sort pch 2 collaborates with cmt 1 to proofread meiotic homolog interactions
url https://doi.org/10.1371/journal.pgen.1008904
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AT needhibhalla pch2collaborateswithcmt1toproofreadmeiotichomologinteractions