Ime2p and Cdc28p: Co‐pilots driving meiotic development

Honigberg, Saul M.

doi:10.1002/jcb.20131

Cited by 36 publications

(44 citation statements)

References 63 publications

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“…The N. crassa genome does not contain an IME1 homolog, but does have one homolog of IME2 (NCU01498) (Borkovich et al 2004). IME2 is a serine-threonine protein kinase that regulates the expression and activity of many early and late meiotic genes; ime2 mutants do not sporulate (Smith and Mitchell 1989;Honigberg 2004). In contrast to S. cerevisiae ime2 mutants, homozygous crosses between N. crassa strains containing a deletion in NCU01498 (ime-2) were fertile and exhibited no sexual cycle defects ( Figure 7A).…”

Section: Resultsmentioning

confidence: 99%

Meiotic Regulators Ndt80 and Ime2 Have Different Roles in Saccharomyces and Neurospora

Hutchison

Glass

2010

Genetics

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Meiosis is a highly regulated process in eukaryotic species. The filamentous fungus Neurospora crassa has been shown to be missing homologs of a number of meiotic initiation genes conserved in Saccharomyces cerevisiae, but has three homologs of the well-characterized middle meiotic transcriptional regulator NDT80. In this study, we evaluated the role of all three NDT80 homologs in the formation of female reproductive structures, sexual development, and meiosis. We found that none of the NDT80 homologs were required for meiosis and that even the triple mutant was unaffected. However, strains containing mutations in NCU09915 (fsd-1) were defective in female sexual development and ascospore maturation. vib-1 was a major regulator of protoperithecial development in N. crassa, and double mutants carrying deletions of both vib-1 (NCU03725) and fsd-1 exhibited a synergistic effect on the timing of female reproductive structure (protoperithecia) formation. We further evaluated the role of the N. crassa homolog of IME2, a kinase involved in initiation of meiosis in S. cerevisiae. Strains containing mutations in ime-2 showed unregulated development of protoperithecia. Genetic analysis indicated that mutations in vib-1 were epistatic to ime-2, suggesting that IME-2 may negatively regulate VIB-1 activity. Our data indicate that the IME2/NDT80 pathway is not involved in meiosis in N. crassa, but rather regulates the formation of female reproductive structures.

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Section: Resultsmentioning

confidence: 99%

Meiotic Regulators Ndt80 and Ime2 Have Different Roles in Saccharomyces and Neurospora

Hutchison

Glass

2010

Genetics

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“…The meiotic division is a differentiation program precisely controlled by the action of protein kinases (34). Regulatory circuits check the occurrence of the specific meiotic division (meiose I) that should be coordinated with DNA replication and recombination to produce the correct segregation of homologous chromosomes into the gametes (35).…”

Section: Discussionmentioning

confidence: 99%

Dual Role of the Cdc7-regulatory Protein Dbf4 during Yeast Meiosis

Valentin

Schwob

Seta

2006

Journal of Biological Chemistry

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The Dbf4-dependent Cdc7 kinase (DDK) is essential for chromosome duplication in all eukaryotes, but was proposed to be dispensable for yeast pre-meiotic DNA replication. This discrepancy led us to investigate the role of the unstable Cdc7-regulatory protein Dbf4 in meiosis. We show that, when Dbf4 is depleted at the time of meiotic induction, cells enter the meiotic program but do not replicate their chromosomes. Surprisingly when Dbf4 is depleted after the initiation of DNA synthesis, S phase goes to completion, but most cells arrest before anaphase I. Deletion of the cohesin Rec8 suppresses this phenotype, suggesting a distinct role of DDK for meiotic chromosome segregation. As after Cdc5 depletion, a fraction of cells undergo a single equational division suggesting a failure to mono-orient sister kinetochores. Our results demonstrate that Dbf4 is essential for DNA replication during meiosis like in vegetative cells and provide evidence for an additional role in setting up the reductional division of meiosis I.The initiation of eukaryotic DNA replication requires the activation of two Ser/Thr protein kinases, an S phase cyclin-dependent kinase (CDK) 3 and a Dbf4-dependent kinase (DDK), named Cdc7 in budding yeast (1). The Cdc7-Dbf4 kinase, which is conserved from yeast to human (2), is responsible for a late step in replication origin firing, locally and throughout S phase (3, 4). Cdc7-Dbf4 is also a target and transducer of the ATR-dependent S phase checkpoint in yeast and vertebrates (5, 6). Besides its role in origin firing, Cdc7 has also been implicated in induced mutagenesis and meiotic recombination (2). Dbf4 is the Cdc7 kinase regulatory subunit, an unstable protein that accumulates in late G 1 , binds to replication origins, and guides Cdc7 kinase activity toward specific subunits of the pre-initiation complex (7-10).Despite its well characterized function for DNA replication in the mitotic cell cycle, little is known on the role of DDK during meiosis. Original experiments using a temperature-sensitive cdc7 allele concluded that it was essential neither for pre-meiotic DNA replication nor for ARS1 origin firing (11, 12), leading to the idea that the mechanisms controlling DNA replication could be different in mitosis and meiosis. Hence several conserved initiation proteins (SpCdc18/Cdc6, Mcm2, and Mcm4) were found dispensable for pre-meiotic S phase in fission yeast (13), but more recent results using tighter mutants did not confirm this conclusion (14 -16). Furthermore, the same replication origins are generally used in mitosis and meiosis and acted upon by the same CDK complex in both cell types (17-21). In fact, Cdc7's dispensability for meiotic replication appeared as an exception and its precise function deserved further examination.In this paper we reinvestigate the role of Cdc7-Dbf4 during meiosis. Contrary to initial reports, we show that Dbf4 is essential for pre-meiotic DNA replication and that no DNA synthesis occurs in its absence, as observed in mitosis. Furthermore we provide evidence t...

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“…Genetic studies have shown that Ime2 regulates multiple steps in meiotic development, including pre-meiotic S-phase and entry into the meiotic divisions, as well as the transcriptional program of meiosis at the early and middle phases (10). In addition, it has been suggested that Ime2 can regulate exit from MI (23).…”

Section: Discussionmentioning

confidence: 99%

Arg-Pro-X-Ser/Thr Is a Consensus Phosphoacceptor Sequence for the Meiosis-Specific Ime2 Protein Kinase in Saccharomyces cerevisiae

et al. 2006

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Ime2 is a meiosis-specific protein kinase in Saccharomyces cerevisiae that is functionally related to cyclin-dependent kinase. Although Ime2 regulates multiple steps in meiosis, only a few of its substrates have been identified. Here we show that Ime2 phosphorylates Sum1, a repressor of meiotic gene transcription, on Thr-306. Ime2 protein kinase assays on Sum1 mutants and synthetic peptides define a consensus motif Arg-Pro-X-Ser/Thr that is required for efficient phosphorylation by Ime2. The carboxyl residue adjacent to the phosphoacceptor (+1 position) also influences the efficiency of Ime2 phosphorylation with alanine being a preferred residue. This information has predictive value in identifying new potential Ime2 targets as shown by the ability of Ime2 to phosphorylate Sgs1 and Gip1 in vitro, and could be important in differentiating mitotic and meiotic regulatory pathways. Keywordsyeast; meiosis; protein kinase; Ime2; Sum1; consensus phosphorylation site Meiosis is a specialized form of cell division that produces the haploid cells required for sexual reproduction. It is characterized by DNA replication, high levels of genetic recombination, and two sequential rounds of chromosome segregation. These processes require the choreographed expression of meiosis-specific genes in a transcriptional cascade (11,31). In the budding yeast Saccharomyces cerevisiae, meiosis is induced by nutrient depletion and is coupled to spore formation. Starvation for key nutrients induces expression of the early gene transcriptional activator Ime1 (12). One of the genes activated by Ime1 encodes Ime2, a serine/threonine kinase that is functionally related to the Cdc28 cyclin-dependent kinase (CDK) and which shows similarity to the CMGC-group of protein kinases (10). Ime2 is required for critical events in meiosis, including the replication of DNA, the regulation of meiotic gene expression, and the meiotic divisions. † This work was supported by grants from the National Institutes of Health to Andrew Vershon (GM 58762) and Edward Winter GM (GM061817).*>To whom correspondence should be addressed: 233 South 10th St., Philadelphia, PA 19107. Phone:(215) 923-9162. E-mail: edward.winter@jefferson.edu.. Π These authors contributed equally to this work. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe role that Ime2 plays in regulating meiotic S phase is related to that of Cdc28 in triggering Sphase in mitosis. In both mitosis and meiosis the G 1 -S transition is prohibited by the Clb5,6/ Cdc28 inhibitor Sic1 (24). Entry into S phase is delayed until Sic1 is phosphorylated, a reaction catalyzed in mitosis by Cdc28 in complex with the G 1 -phase cyclins Cln1 and Cln2 (15,30). In meiosis, Ime2 is required for Sic1 degradation and DNA replication (7). Others have recently demonstrated that Ime2 directly phosphorylates multiple sites in Sic1 in vitro. This is insufficient to trigger meiotic Sic1 destruction, however, suggesting that Ime2 does not simply replace the function of Cln1,2-/Cdc28 in meiosis to ...

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Ime2p and Cdc28p: Co‐pilots driving meiotic development

Cited by 36 publications

References 63 publications

Meiotic Regulators Ndt80 and Ime2 Have Different Roles in Saccharomyces and Neurospora

Meiotic Regulators Ndt80 and Ime2 Have Different Roles in Saccharomyces and Neurospora

Dual Role of the Cdc7-regulatory Protein Dbf4 during Yeast Meiosis

Arg-Pro-X-Ser/Thr Is a Consensus Phosphoacceptor Sequence for the Meiosis-Specific Ime2 Protein Kinase in Saccharomyces cerevisiae

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