Resolvases, Dissolvases, and Helicases in Homologous Recombination: Clearing the Road for Chromosome Segregation

San-Segundo, Pedro A.; Clemente‐Blanco, Andrés

doi:10.3390/genes11010071

Cited by 20 publications

(14 citation statements)

References 187 publications

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“…Recombination initiates with the introduction of programmed DNA double-strand breaks (DSBs) catalyzed by Spo11 and its associated proteins [1]. These breaks are then processed and repaired, part of them as crossovers (CO) [2], to establish physical connections between homologous chromosomes essential to direct their proper segregation [3]. As recombination proceeds, chromosome synapsis occurs by the polymerization of the synaptonemal complex (SC) connecting the axes of paired homologs.…”

Section: Introductionmentioning

confidence: 99%

Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm

et al. 2021

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“…These breaks are then processed and repaired, part of them as crossovers (CO) (Allers and Lichten, 2001), to establish physical connections between homologous chromosomes essential to direct their proper segregation (San-Segundo and Clemente-Blanco, 2020). In parallel to recombination, chromosome synapsis occurs by the polymerization of the synaptonemal complex (SC) connecting the axes of paired homologs.…”

Section: Introductionmentioning

confidence: 99%

Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm

Herruzo

Lago-Maciel

Baztán

et al. 2021

Preprint

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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 NES or 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.

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“…Meiosis is a special form of cell division that lies at the heart of gametogenesis in most sexually reproducing organisms. During meiosis, a series of complex DNA and chromosome interactions culminate in the accurate segregation of a haploid complement of chromosomes to the gametes (Keeney et al, 2014;Hunter, 2015;Zickler and Kleckner, 2015;San-Segundo and Clemente-Blanco, 2020). Chromatin remodeling events, including histone posttranslational modifications and incorporation of histone variants, play important roles in several processes during meiotic development (Brachet et al, 2012;Yamada and Ohta, 2013;Crichton et al, 2014;Ontoso et al, 2014;Yamada et al, 2018a).…”

Section: Introductionmentioning

confidence: 99%

SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion

González-Arranz

Gardner

et al. 2020

Front. Cell Dev. Biol.

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The H2A.Z histone variant is deposited into the chromatin by the SWR1 complex, affecting multiple aspects of meiosis. We describe here a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the linker of nucleoskeleton, and cytoskeleton (LINC) complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton, promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during the meiotic prophase is reduced in the htz1 mutant lacking H2A.Z, but it is unaffected in swr1 cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

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Resolvases, Dissolvases, and Helicases in Homologous Recombination: Clearing the Road for Chromosome Segregation

Cited by 20 publications

References 187 publications

Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm

Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm

Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm

SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion

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