Functional Impact of the H2A.Z Histone Variant During Meiosis in <i>Saccharomyces cerevisiae</i>

González-Arranz, Sara; Cavero, Santiago; Morillo-Huesca, Macarena; Andújar, Eloísa; Pérez-Alegre, Mónica; Prado, Félix; San-Segundo, Pedro A.

doi:10.1534/genetics.118.301110

Cited by 16 publications

(19 citation statements)

References 81 publications

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“…Contrary to current understanding, we find that the Pch2-Hop1 module 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 [7, 8]. Based on our data and on the effect of Pch2 on HORMA topology [9–11], we propose that Pch2 promotes checkpoint proficiency by catalyzing the availability of signaling-competent Hop1.…”

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confidence: 78%

Homeostatic control of meiotic G2/prophase checkpoint function by Pch2 and Hop1

Raina

Vader

2020

Preprint

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17 Checkpoints cascades coordinate cell cycle progression with essential chromosomal 18 processes. During meiotic G2/prophase, recombination and chromosome synapsis are 19 monitored by what are considered distinct checkpoints [1-3]. In budding yeast, the AAA+ 20 ATPase Pch2 is thought to specifically promote cell cycle delay in response to synapsis defects 21 [4-6]. However, unperturbed pch2D cells are delayed in meiotic G2/prophase [6], suggesting 22 paradoxical roles for Pch2 in cell cycle progression. Here, we provide insight into the checkpoint 23 roles of Pch2 and its connection to Hop1, a HORMA domain-containing client protein. 24 Contrary to current understanding, we find that the Pch2-Hop1 module is crucial for 25 checkpoint function in response to both recombination and synapsis defects, thus revealing a 26 shared meiotic checkpoint cascade. Meiotic checkpoint responses are transduced by DNA 27 break-dependent phosphorylation of Hop1 [7, 8]. Based on our data and on the effect of Pch2 28 on HORMA topology [9-11], we propose that Pch2 promotes checkpoint proficiency by 29 catalyzing the availability of signaling-competent Hop1. Conversely, we demonstrate that Pch2 30 can act as a checkpoint silencer, also in the face of persistent DNA repair defects. We establish 31 a framework in which Pch2 and Hop1 form a homeostatic module that governs general meiotic 32 checkpoint function. We show that this module can -depending on the cellular context -fuel 33 or extinguish meiotic checkpoint function, which explains the contradictory roles of Pch2 in cell 34 cycle control. Within the meiotic checkpoint, the Pch2-Hop1 module thus operates analogous 35 to the Pch2/TRIP13-Mad2 module in the spindle assembly checkpoint that monitors 36 chromosome segregation [12-16]. 37 38 repair 40 41 Results and discussion 42 43 Feedback regulation between Hop1, Zip1 and Pch2 influences SC assembly 44 In G2/prophase of the meiotic program, double strand break (DSB) formation 45 recombinational repair, synapsis of homologous chromosomes is integrated with cell cycle 46 progression [17]. In budding yeast, Zip1-mediated Synaptonemal Complex (SC) assembly promotes 47 cell cycle progression by regulating chromosome-based checkpoint activity [18-20]. The 48 chromosome axis, of which Hop1 is a key component, forms the structural foundation for recruitment 49 of the SC [21]. The functionality of meiotic checkpoints that monitor recombination and synapsis is 50 linked to successful recombination and SC establishment, and the function of Pch2 is associated with 51 both Hop1 and Zip1: Hop1 is a client of Pch2 [22][23][24][25], and chromosomal association of Pch2 is tightly 52 linked to Zip1/SC establishment [5, 20, 23,[26][27][28][29]. To understand the wiring between these numerous 53 crucial events during meiotic G2/prophase and the role of Pch2 herein, we initially investigated SC 54 formation and its relation to Pch2, Hop1 and Zip1. 55 SC components, like Zip1, can form extrachromosomal aggregates known as polycomplexes 56 (PCs) [4]. Cells ...

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confidence: 78%

Homeostatic control of meiotic G2/prophase checkpoint function by Pch2 and Hop1

Raina

Vader

2020

Preprint

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“…H2A.Z is lost (Gonzalez-Arranz et al, 2018), but H2A.Z foci persisted in the absence of the SWR1 complex, as seen in enhanced images (Figures 1B,C). Double staining with Zip1 antibodies, as a marker of synapsed chromosomes, showed that these SWR1-independent H2A.Z foci were primarily located at chromosome ends ( Figure 1B); 65.4% of the swr1 spread pachytene nuclei scored (n = 26) displayed H2A.Z at telomeres.…”

Section: H2az Remains At Chromosome Ends In the Absence Of Swr1mentioning

confidence: 78%

“…Our previous cytological studies have shown that H2A.Z extensively decorates meiotic chromatin in wild-type pachytene chromosomes, except in the ribosomal DNA (rDNA) region where its presence is markedly reduced (Gonzalez-Arranz et al, 2018). In the swr1 mutant, the bulk of chromatin-associated FIGURE 1 | H2A.Z localizes to chromosome ends during meiotic prophase I.…”

Section: H2az Remains At Chromosome Ends In the Absence Of Swr1mentioning

confidence: 97%

“…All the strains are isogenic to the BR1919 background (Rockmill and Roeder, 1990). The swr1::natMX4, swr1::hphMX4, ndj1::natMX4, ndj1::kanMX6, htz1::natMX4, mps3::natMX4, and mps3::hphMX4 gene deletions were made using a PCR-based approach (Longtine et al, 1998;Goldstein and McCusker, 1999). The htz1::URA3 deletion and the functional HTZ1-GFP construct were previously described (Gonzalez-Arranz et al, 2018).…”

Section: Yeast Strainsmentioning

confidence: 99%

“…The swr1::natMX4, swr1::hphMX4, ndj1::natMX4, ndj1::kanMX6, htz1::natMX4, mps3::natMX4, and mps3::hphMX4 gene deletions were made using a PCR-based approach (Longtine et al, 1998;Goldstein and McCusker, 1999). The htz1::URA3 deletion and the functional HTZ1-GFP construct were previously described (Gonzalez-Arranz et al, 2018). The MPS3-GFP, MPS3-3HA, NET1-RedStar2, SPC110-RedStar2, SPC110-mCherry, CNM67-mCherry, HOP1-mCherry, and PMA1-mCherry gene tagging constructs were also made by PCR (Longtine et al, 1998;Janke et al, 2004;Sheff and Thorn, 2004).…”

Section: Yeast Strainsmentioning

confidence: 99%

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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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Immediate visualization of recombination events and chromosome segregation defects in fission yeast meiosis

Roca

Lorenz

2019

Chromosoma

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Schizosaccharomyces pombe, also known as fission yeast, is an established model for studying chromosome biological processes. Over the years, research employing fission yeast has made important contributions to our knowledge about chromosome segregation during meiosis, as well as meiotic recombination and its regulation. Quantification of meiotic recombination frequency is not a straightforward undertaking, either requiring viable progeny for a genetic plating assay, or relying on laborious Southern blot analysis of recombination intermediates. Neither of these methods lends itself to high-throughput screens to identify novel meiotic factors. Here, we establish visual assays novel to Sz. pombe for characterizing chromosome segregation and meiotic recombination phenotypes. Genes expressing red, yellow, and/or cyan fluorophores from spore-autonomous promoters have been integrated into the fission yeast genomes, either close to the centromere of chromosome 1 to monitor chromosome segregation, or on the arm of chromosome 3 to form a genetic interval at which recombination frequency can be determined. The visual recombination assay allows straightforward and immediate assessment of the genetic outcome of a single meiosis by epi-fluorescence microscopy without requiring tetrad dissection. We also demonstrate that the recombination frequency analysis can be automatized by utilizing imaging flow cytometry to enable high-throughput screens. These assays have several advantages over traditional methods for analyzing meiotic phenotypes.Electronic supplementary materialThe online version of this article (10.1007/s00412-019-00691-y) contains supplementary material, which is available to authorized users.

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Functional Impact of the H2A.Z Histone Variant During Meiosis in Saccharomyces cerevisiae

Cited by 16 publications

References 81 publications

Homeostatic control of meiotic G2/prophase checkpoint function by Pch2 and Hop1

Homeostatic control of meiotic G2/prophase checkpoint function by Pch2 and Hop1

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

Immediate visualization of recombination events and chromosome segregation defects in fission yeast meiosis

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