LAB-1 Targets PP1 and Restricts Aurora B Kinase upon Entrance into Meiosis to Promote Sister Chromatid Cohesion

Tzur, Yonatan B; Carvalho, Carlos Egydio de; Nadarajan, Saravanapriah; Bostelen, Ivo van; Gu, Yanjie; Chu, Diana S.; Cheeseman, Iain M.; Colaiácovo, Mónica P.

doi:10.1371/journal.pbio.1001378

Cited by 57 publications

(89 citation statements)

References 87 publications

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“…In wild-type male germ lines, RAD-51 foci are largely disassembled by mid pachytene ( Figure S1), reflecting repair. In contrast, rec-8; coh-3/4 male germ lines had abundant RAD-51 foci that persisted throughout meiotic prophase (Figure 4,A and B), suggesting that as in hermaphrodites (Tzur et al 2012), DSB repair is impaired in males lacking meiotic kleisins. To determine whether RAD-51 disassembly is compromised on the X chromosome in rec-8; coh-3/4 male germ lines, we compared the number of RAD-51 foci on the X chromosome in wild-type vs. rec-8; coh-3/4 males ( Figure 4B).…”

Section: Resultsmentioning

confidence: 99%

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Pseudosynapsis and Decreased Stringency of Meiotic Repair Pathway Choice on the Hemizygous Sex Chromosome of Caenorhabditis elegans Males

Checchi¹,

Lawrence

Van

et al. 2014

Genetics

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During meiosis, accurate chromosome segregation relies on homology to mediate chromosome pairing, synapsis, and crossover recombination. Crossovers are dependent upon formation and repair of double-strand breaks (DSBs) by homologous recombination (HR). In males of many species, sex chromosomes are largely hemizygous, yet DSBs are induced along nonhomologous regions. Here we analyzed the genetic requirements for meiotic DSB repair on the completely hemizygous X chromosome of Caenorhabditis elegans males. Our data reveal that the kinetics of DSB formation, chromosome pairing, and synapsis are tightly linked in the male germ line. Moreover, DSB induction on the X is concomitant with a brief period of pseudosynapsis that may allow X sister chromatids to masquerade as homologs. Consistent with this, neither meiotic kleisins nor the SMC-5/6 complex are essential for DSB repair on the X. Furthermore, early processing of X DSBs is dependent on the CtIP/Sae2 homolog COM-1, suggesting that as with paired chromosomes, HR is the preferred pathway. In contrast, the X chromosome is refractory to feedback mechanisms that ensure crossover formation on autosomes. Surprisingly, neither RAD-54 nor BRC-2 are essential for DSB repair on the X, suggesting that unlike autosomes, the X is competent for repair in the absence of HR. When both RAD-54 and the structure-specific nuclease XPF-1 are abrogated, X DSBs persist, suggesting that single-strand annealing is engaged in the absence of HR. Our findings indicate that alteration in sister chromatid interactions and flexibility in DSB repair pathway choice accommodate hemizygosity on sex chromosomes.

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Section: Resultsmentioning

confidence: 99%

“…To investigate this, we first monitored the localization of the meiotic kleisins REC-8 and COH-3, which are essential for SCC during meiosis (Severson et al 2009;Tzur et al 2012). In hermaphrodites, REC-8 is nucleoplasmic in mitotic germ cells and localizes to chromatin in early meiotic prophase (Pasierbek et al 2001;Severson et al 2009).…”

Section: Resultsmentioning

confidence: 99%

Pseudosynapsis and Decreased Stringency of Meiotic Repair Pathway Choice on the Hemizygous Sex Chromosome of Caenorhabditis elegans Males

Checchi¹,

Lawrence

Van

et al. 2014

Genetics

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“…In contrast, COH-3/4 complexes are only detected in meiotic nuclei following the completion of S-phase, their ability to provide cohesion requires DSBs, and their loading is independent of HTP-3 and TIM-1 (Severson and Meyer, 2014: PMID 25171895). Loss of cohesion, evidenced by extensive separation of sister chromatids in diakinesis oocytes, is observed in mutants lacking REC-8, COH-3 and COH-4 but not in rec-8 single or coh-3 coh-4 double mutants (Severson et al, 2009: PMID 19574299; Tzur et al, 2012: PMID 22927794; Severson and Meyer, 2014: PMID 25171895), demonstrating that both REC-8 and COH-3/4 complexes contribute to sister chromatid cohesion.…”

Section: Meiotic Chromosome Structurementioning

confidence: 99%

Meiosis

et al. 2017

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Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome content in the next generation. This reduction in genetic content is accomplished during a specialized cell division called meiosis, in which two rounds of chromosome segregation follow a single round of DNA replication. In preparation for the first meiotic division, homologous chromosomes pair and synapse, creating a context that promotes formation of crossover recombination events. These crossovers, in conjunction with sister chromatid cohesion, serve to connect the two homologs and facilitate their segregation to opposite poles during the first meiotic division. During the second meiotic division, which is similar to mitosis, sister chromatids separate; the resultant products are haploid cells that become gametes. In C. elegans (and most other eukaryotes) homologous pairing and recombination are required for proper chromosome inheritance during meiosis; accordingly, the events of meiosis are tightly coordinated to ensure the proper execution of these events. In this chapter, we review the seminal events of meiosis: pairing of homologous chromosomes; the changes in chromosome structure that chromosomes undergo during meiosis; the events of meiotic recombination; the differentiation of homologous chromosome pairs into structures optimized for proper chromosome segregation at Meiosis I; and the ultimate segregation of chromosomes during the meiotic divisions. We also review the regulatory processes that ensure the coordinated execution of these meiotic events during prophase I.

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“…However, chromosomes in rec-8 mutants still undergo extensive synapsis, although it does not appear to be fully normal and may involve some intersister or nonhomologous synapsis (14,17,62,63) (see below in this paragraph). Thus, we analyzed the organization of COH-3/4 cohesin complexes in the absence of REC-8.…”

Section: Averaging Over Many Samples Increases the Precision Of Supermentioning

confidence: 99%

Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact Caenorhabditis elegans tissue

Köhler

Wojcik

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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When cells enter meiosis, their chromosomes reorganize as linear arrays of chromatin loops anchored to a central axis. Meiotic chromosome axes form a platform for the assembly of the synaptonemal complex (SC) and play central roles in other meiotic processes, including homologous pairing, recombination, and chromosome segregation. However, little is known about the 3D organization of components within the axes, which include cohesin complexes and additional meiosis-specific proteins. Here, we investigate the molecular organization of meiotic chromosome axes in Caenorhabditis elegans through STORM (stochastic optical reconstruction microscopy) and PALM (photo-activated localization microscopy) superresolution imaging of intact germ-line tissue. By tagging one axis protein (HIM-3) with a photoconvertible fluorescent protein, we established a spatial reference for other components, which were localized using antibodies against epitope tags inserted by CRISPR/Cas9 genome editing. Using 3D averaging, we determined the position of all known components within synapsed chromosome axes to high spatial precision in three dimensions. We find that meiosis-specific HORMA domain proteins span a gap between cohesin complexes and the central region of the SC, consistent with their essential roles in SC assembly. Our data further suggest that the two different meiotic cohesin complexes are distinctly arranged within the axes: Although cohesin complexes containing the kleisin REC-8 protrude above and below the plane defined by the SC, complexes containing COH-3 or -4 kleisins form a central core, which may physically separate sister chromatids. This organization may help to explain the role of the chromosome axes in promoting interhomolog repair of meiotic double-strand breaks by inhibiting intersister repair.

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LAB-1 Targets PP1 and Restricts Aurora B Kinase upon Entrance into Meiosis to Promote Sister Chromatid Cohesion

Abstract: At the onset of the first meiotic division, the protein LAB-1 recruits the PP1 phosphatase to cohesion complexes, preventing Aurora B kinase from targeting cohesins for degradation prematurely and thereby ensuring proper progression of meiotic events in C. elegans.

Cited by 57 publications

References 87 publications

Pseudosynapsis and Decreased Stringency of Meiotic Repair Pathway Choice on the Hemizygous Sex Chromosome of Caenorhabditis elegans Males

Pseudosynapsis and Decreased Stringency of Meiotic Repair Pathway Choice on the Hemizygous Sex Chromosome of Caenorhabditis elegans Males

Meiosis

Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact Caenorhabditis elegans tissue

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