Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.

During meiosis, defects in critical events trigger checkpoint activation and restrict cell cycle progression. The budding yeast Pch2 AAA+ ATPase orchestrates the checkpoint response launched by synapsis deficiency; deletion of PCH2 or mutation of the ATPase catalytic sites suppress the meiotic block...

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Autores principales:	Esther Herruzo, Ana Lago-Maciel, Sara Baztán, Beatriz Santos, Jesús A Carballo, Pedro A San-Segundo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/bac9f12a83d149aeafe0e4e147a43d54
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spelling	oai:doaj.org-article:bac9f12a83d149aeafe0e4e147a43d542021-12-02T20:02:45ZPch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.1553-73901553-740410.1371/journal.pgen.1009560https://doaj.org/article/bac9f12a83d149aeafe0e4e147a43d542021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009560https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404During meiosis, defects in critical events trigger checkpoint activation and restrict cell cycle progression. The budding yeast Pch2 AAA+ ATPase orchestrates the checkpoint response launched by synapsis deficiency; deletion of PCH2 or mutation of the ATPase catalytic sites suppress the meiotic block of the zip1Δ mutant lacking the central region of the synaptonemal complex. Pch2 action enables adequate levels of phosphorylation of the Hop1 axial component at threonine 318, which in turn promotes activation of the Mek1 effector kinase and the ensuing checkpoint response. In zip1Δ chromosomes, Pch2 is exclusively associated to the rDNA region, but this nucleolar fraction is not required for checkpoint activation, implying that another yet uncharacterized Pch2 population must be responsible for this function. Here, we have artificially redirected Pch2 to different subcellular compartments by adding ectopic Nuclear Export (NES) or Nuclear Localization (NLS) sequences, or by trapping Pch2 in an immobile extranuclear domain, and we have evaluated the effect on Hop1 chromosomal distribution and checkpoint activity. We have also deciphered the spatial and functional impact of Pch2 regulators including Orc1, Dot1 and Nup2. We conclude that the cytoplasmic pool of Pch2 is sufficient to support the meiotic recombination checkpoint involving the subsequent Hop1-Mek1 activation on chromosomes, whereas the nuclear accumulation of Pch2 has pathological consequences. We propose that cytoplasmic Pch2 provokes a conformational change in Hop1 that poises it for its chromosomal incorporation and phosphorylation. Our discoveries shed light into the intricate regulatory network controlling the accurate balance of Pch2 distribution among different cellular compartments, which is essential for proper meiotic outcomes.Esther HerruzoAna Lago-MacielSara BaztánBeatriz SantosJesús A CarballoPedro A San-SegundoPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 7, p e1009560 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Esther Herruzo Ana Lago-Maciel Sara Baztán Beatriz Santos Jesús A Carballo Pedro A San-Segundo Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.
description	During meiosis, defects in critical events trigger checkpoint activation and restrict cell cycle progression. The budding yeast Pch2 AAA+ ATPase orchestrates the checkpoint response launched by synapsis deficiency; deletion of PCH2 or mutation of the ATPase catalytic sites suppress the meiotic block of the zip1Δ mutant lacking the central region of the synaptonemal complex. Pch2 action enables adequate levels of phosphorylation of the Hop1 axial component at threonine 318, which in turn promotes activation of the Mek1 effector kinase and the ensuing checkpoint response. In zip1Δ chromosomes, Pch2 is exclusively associated to the rDNA region, but this nucleolar fraction is not required for checkpoint activation, implying that another yet uncharacterized Pch2 population must be responsible for this function. Here, we have artificially redirected Pch2 to different subcellular compartments by adding ectopic Nuclear Export (NES) or Nuclear Localization (NLS) sequences, or by trapping Pch2 in an immobile extranuclear domain, and we have evaluated the effect on Hop1 chromosomal distribution and checkpoint activity. We have also deciphered the spatial and functional impact of Pch2 regulators including Orc1, Dot1 and Nup2. We conclude that the cytoplasmic pool of Pch2 is sufficient to support the meiotic recombination checkpoint involving the subsequent Hop1-Mek1 activation on chromosomes, whereas the nuclear accumulation of Pch2 has pathological consequences. We propose that cytoplasmic Pch2 provokes a conformational change in Hop1 that poises it for its chromosomal incorporation and phosphorylation. Our discoveries shed light into the intricate regulatory network controlling the accurate balance of Pch2 distribution among different cellular compartments, which is essential for proper meiotic outcomes.
format	article
author	Esther Herruzo Ana Lago-Maciel Sara Baztán Beatriz Santos Jesús A Carballo Pedro A San-Segundo
author_facet	Esther Herruzo Ana Lago-Maciel Sara Baztán Beatriz Santos Jesús A Carballo Pedro A San-Segundo
author_sort	Esther Herruzo
title	Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.
title_short	Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.
title_full	Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.
title_fullStr	Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.
title_full_unstemmed	Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.
title_sort	pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/bac9f12a83d149aeafe0e4e147a43d54
work_keys_str_mv	AT estherherruzo pch2orchestratesthemeioticrecombinationcheckpointfromthecytoplasm AT analagomaciel pch2orchestratesthemeioticrecombinationcheckpointfromthecytoplasm AT sarabaztan pch2orchestratesthemeioticrecombinationcheckpointfromthecytoplasm AT beatrizsantos pch2orchestratesthemeioticrecombinationcheckpointfromthecytoplasm AT jesusacarballo pch2orchestratesthemeioticrecombinationcheckpointfromthecytoplasm AT pedroasansegundo pch2orchestratesthemeioticrecombinationcheckpointfromthecytoplasm
_version_	1718375682389573632

Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.

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