Mek1 Kinase Governs Outcomes of Meiotic Recombination and the Checkpoint Response

Wu, Hsin Yen; Ho, Hsuan-Chung; Burgess, Sean M.

doi:10.1016/j.cub.2010.09.016

Cited by 39 publications

(71 citation statements)

References 62 publications

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“…The mek1-as mutation did not significantly affect the spore viability of either single mutant alone (Table 4). The MEK1-GST allele increased spore viability in pch2D spo11-HA strains from 57 to 89% (P , 0.005); however, as described previously (Wu et al 2010), there was a general defect in spore formation due to MEK1-GST. MEK1-GST did not increase the spore viability in either single mutant (Table 4).…”

Section: And Alani 2009mentioning

confidence: 69%

“…Wu et al (2010) recently showed that MEK1-GST is a semidominant allele that shows increased interhomolog recombination events, primarily noncrossovers, and fewer intersister events, with no change in DSB levels. As shown in Table 4, we constructed mek1-as pch2D spo11-HA and MEK1-GST pch2D spo11-HA strains and examined their spore formation efficiency and viability (mek1-as strains were analyzed in the absence of a 1-Na-PP1 inhibitor).…”

Section: And Alani 2009mentioning

confidence: 99%

“…Alternatively, reinforcing interhomolog bias should suppress the pch2D spo11-HA phenotype. To test this hypothesis, we utilized two MEK1 alleles: mek1-as (mek1-Q241G hypomorph) (Callender and Hollingsworth 2010) and MEK1-GST (hypermorph) (Wu et al 2010). mek1-as strains complete meiosis efficiently in the absence of a 1-Na-PP1 inhibitor and display nearly wild-type spore viability; however, Mek1-as has reduced affinity for ATP in vitro, and in one dmc1D strain background, the mek1-as Wild-type (NH942/NH943), pch2D (EAY2209/EAY2210), and pch2D rad54D (EAY2681/ EAY2685) strains were sporulated and analyzed for segregation of genetic markers in the NH942/NH943 strain background.…”

Section: And Alani 2009mentioning

confidence: 99%

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Pch2 Modulates Chromatid Partner Choice During Meiotic Double-Strand Break Repair in Saccharomyces cerevisiae

Zanders¹,

Brown

Chen

et al. 2011

Genetics

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In most organisms, the segregation of chromosomes during the first meiotic division is dependent upon at least one crossover (CO) between each pair of homologous chromosomes. COs can result from chromosome double-strand breaks (DSBs) that are induced and preferentially repaired using the homologous chromosome as a template. The PCH2 gene of budding yeast is required to establish proper meiotic chromosome axis structure and to regulate meiotic interhomolog DSB repair outcomes. These roles appear conserved in the mouse ortholog of PCH2, Trip13, which is also involved in meiotic chromosome axis organization and the regulation of DSB repair. Using a combination of genetic and physical assays to monitor meiotic DSB repair, we present data consistent with pch2D mutants showing defects in suppressing intersister DSB repair. These defects appear most pronounced in dmc1D mutants, which are defective for interhomolog repair, and explain the previously reported observation that pch2D dmc1D cells can complete meiosis. Results from genetic epistasis analyses involving spo13D, rad54D, and mek1/MEK1 alleles and an intersister recombination reporter assay are also consistent with Pch2 acting to limit intersister repair. We propose a model in which Pch2 is required to promote full Mek1 activity and thereby promotes interhomolog repair.

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Section: And Alani 2009mentioning

confidence: 69%

Section: And Alani 2009mentioning

confidence: 99%

Section: And Alani 2009mentioning

confidence: 99%

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Pch2 Modulates Chromatid Partner Choice During Meiotic Double-Strand Break Repair in Saccharomyces cerevisiae

Zanders¹,

Brown

Chen

et al. 2011

Genetics

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“…Analysis of crossover (CO) and noncrossover (NCO) products of recombination was carried out by digesting purified genomic DNA with XhoI, or XhoI and NgoMIV, respectively (Oh et al 2009;Wu et al 2010). The reported CO and NCO are based on measurements from three independent colonies.…”

Section: Dna Analysismentioning

confidence: 99%

The Nucleoporin Nup2 Contains a Meiotic-Autonomous Region that Promotes the Dynamic Chromosome Events of Meiosis

Chu

Gromova²,

Newman³

et al. 2017

Genetics

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Meiosis is a specialized cellular program required to create haploid gametes from diploid parent cells. Homologous chromosomes pair, synapse, and recombine in a dynamic environment that accommodates gross chromosome reorganization and significant chromosome motion, which are critical for normal chromosome segregation. In Saccharomyces cerevisiae, Ndj1 is a meiotic telomere-associated protein required for physically attaching telomeres to proteins embedded in the nuclear envelope. In this study, we identified additional proteins that act at the nuclear periphery from meiotic cell extracts, including Nup2, a nonessential nucleoporin with a known role in tethering interstitial chromosomal loci to the nuclear pore complex. We found that deleting NUP2 affects meiotic progression and spore viability, and gives increased levels of recombination intermediates and products. We identified a previously uncharacterized 125 aa region of Nup2 that is necessary and sufficient for its meiotic function, thus behaving as a meiotic autonomous region (MAR). Nup2-MAR forms distinct foci on spread meiotic chromosomes, with a subset overlapping with Ndj1 foci. Localization of Nup2-MAR to meiotic chromosomes does not require Ndj1, nor does Ndj1 localization require Nup2, suggesting these proteins function in different pathways, and their interaction is weak or indirect. Instead, several severe synthetic phenotypes are associated with the nup2D ndj1D double mutant, including delayed turnover of recombination joint molecules, and a failure to undergo nuclear divisions without also arresting the meiotic program. These data suggest Nup2 and Ndj1 support partially overlapping functions that promote two different levels of meiotic chromosome organization necessary to withstand a dynamic stage of the eukaryotic life cycle.

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“…These findings nicely illustrate how core checkpoint functions are interdigitated with meiosis-specific chromosomal processes. It has recently been reported that Mek1 can further modify the checkpoint response by increasing the checkpoint-mediated delay at pachytene (192).…”

Section: Control Of Middle Genes By the Pachytene Checkpoint The Pachmentioning

confidence: 99%

The Sum1/Ndt80 Transcriptional Switch and Commitment to Meiosis in Saccharomyces cerevisiae

Winter

2012

Microbiol Mol Biol Rev

105

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SUMMARY Cells encounter numerous signals during the development of an organism that induce division, differentiation, and apoptosis. These signals need to be present for defined intervals in order to induce stable changes in the cellular phenotype. The point after which an inducing signal is no longer needed for completion of a differentiation program can be termed the “commitment point.” Meiotic development in the yeast Saccharomyces cerevisiae (sporulation) provides a model system to study commitment. Similar to differentiation programs in multicellular organisms, the sporulation program in yeast is regulated by a transcriptional cascade that produces early, middle, and late sets of sporulation-specific transcripts. Although critical meiosis-specific events occur as early genes are expressed, commitment does not take place until middle genes are induced. Middle promoters are activated by the Ndt80 transcription factor, which is produced and activated shortly before most middle genes are expressed. In this article, I discuss the connection between Ndt80 and meiotic commitment. A transcriptional regulatory pathway makes NDT80 transcription contingent on the prior expression of early genes. Once Ndt80 is produced, the recombination (pachytene) checkpoint prevents activation of the Ndt80 protein. Upon activation, Ndt80 triggers a positive autoregulatory loop that leads to the induction of genes that promote exit from prophase, the meiotic divisions, and spore formation. The pathway is controlled by multiple feed-forward loops that give switch-like properties to the commitment transition. The conservation of regulatory components of the meiotic commitment pathway and the recently reported ability of Ndt80 to increase replicative life span are discussed.

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Mek1 Kinase Governs Outcomes of Meiotic Recombination and the Checkpoint Response

Cited by 39 publications

References 62 publications

Pch2 Modulates Chromatid Partner Choice During Meiotic Double-Strand Break Repair in Saccharomyces cerevisiae

Pch2 Modulates Chromatid Partner Choice During Meiotic Double-Strand Break Repair in Saccharomyces cerevisiae

The Nucleoporin Nup2 Contains a Meiotic-Autonomous Region that Promotes the Dynamic Chromosome Events of Meiosis

The Sum1/Ndt80 Transcriptional Switch and Commitment to Meiosis in Saccharomyces cerevisiae

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