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Morphogenesis beyond cytokinetic arrest in Saccharomyces cerevisiae.

Jiménez J, Cid VJ, Cenamor R, Yuste M, Molero G, Nombela C, Sánchez M - J. Cell Biol. (1998)

Bottom Line: This morphogenetic response reflects entry into a new round of the cell cycle: the preference for polarization from the distal pole was lost in bud1 cdc15 double mutants; double cdc15-lyt1 cdc28-4 mutants, defective for START, did not develop apical projections and apical polarization was accompanied by DNA replication.Apical polarization was delayed in cdc15 mutants as compared with budding in control cells and this delay was abolished in a septin mutant.Our results suggest that the delayed M/G1 transition in cdc15 mutants is due to a septin-dependent checkpoint that couples initiation of the cell cycle to the completion of cytokinesis.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Microbiología II, Facultad de Farmacia.

ABSTRACT
The budding yeast lyt1 mutation causes cell lysis. We report here that lyt1 is an allele of cdc15, a gene which encodes a protein kinase that functions late in the cell cycle. Neither cdc15-1 nor cdc15-lyt1 strains are able to septate at 37 degreesC, even though they may manage to rebud. Cells lyse after a shmoo-like projection appears at the distal pole of the daughter cell. Actin polarizes towards the distal pole but the septins remain at the mother-daughter neck. This morphogenetic response reflects entry into a new round of the cell cycle: the preference for polarization from the distal pole was lost in bud1 cdc15 double mutants; double cdc15-lyt1 cdc28-4 mutants, defective for START, did not develop apical projections and apical polarization was accompanied by DNA replication. The same phenomena were caused by mutations in the genes CDC14, DBF2, and TEM1, which are functionally related to CDC15. Apical polarization was delayed in cdc15 mutants as compared with budding in control cells and this delay was abolished in a septin mutant. Our results suggest that the delayed M/G1 transition in cdc15 mutants is due to a septin-dependent checkpoint that couples initiation of the cell cycle to the completion of cytokinesis.

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Hypotheses for the mechanisms involved in the coordination of morphogenetic events at the end of mitosis. Hypothesis  (a) implies that the Cdc15p-mediated pathway is directly or indirectly involved in B cyclin degradation by the APC and that the  consequent inactivation of the Cdc28p–B cyclin complex accounts for the polarization of the morphogenetic apparatus to the  neck area for septum development. Hypothesis (b) argues that  the Cdc15p pathway, similar to the cdc7 pathway in the fission  yeast, would directly trigger the morphogenetic response for septum formation, perhaps activated by signals derived from  Cdc28p–B cyclin inactivation or coordinated with it via feedback  mechanisms (broken line). The arrest in anaphase observed in  cdc15 and related mutants would be due to a cell cycle checkpoint that would inactivate Cdc28p until morphogenetic events at  the neck are settled. The fact that a septin (cdc10) mutation prevents the delay in budding observed in a cdc15 mutant suggest  that the components of such putative checkpoint rely on the integrity of the septin ring for their functionality.
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Figure 9: Hypotheses for the mechanisms involved in the coordination of morphogenetic events at the end of mitosis. Hypothesis (a) implies that the Cdc15p-mediated pathway is directly or indirectly involved in B cyclin degradation by the APC and that the consequent inactivation of the Cdc28p–B cyclin complex accounts for the polarization of the morphogenetic apparatus to the neck area for septum development. Hypothesis (b) argues that the Cdc15p pathway, similar to the cdc7 pathway in the fission yeast, would directly trigger the morphogenetic response for septum formation, perhaps activated by signals derived from Cdc28p–B cyclin inactivation or coordinated with it via feedback mechanisms (broken line). The arrest in anaphase observed in cdc15 and related mutants would be due to a cell cycle checkpoint that would inactivate Cdc28p until morphogenetic events at the neck are settled. The fact that a septin (cdc10) mutation prevents the delay in budding observed in a cdc15 mutant suggest that the components of such putative checkpoint rely on the integrity of the septin ring for their functionality.

Mentions: Lew and Reed (1993) reported that the actin cytoskeleton is not polarized to the septum area to promote cytokinesis until the Cdc28p–Clb2p complex has become dissociated. Here we report that when anaphase arrest persists, a polar budding process is started in the absence of cytokinesis. It could be surmised that the inactivation of the Cdc28p–Clb complex by degradation of B cyclins would be sufficient for the promotion of both nuclear telophase events and cytokinesis and that the Cdc15p pathway would be essential for inactivating the CDK–cyclin complex at this stage. We shall refer to this as the classical hypothesis (Fig. 9 a). Following this interpretation, it is difficult to understand some of our results, such as the overcoming of anaphase arrest in the absence of cytokinesis in cdc15 and, especially, the absence of such an arrest in a double cdc15 cdc10 mutant. A plausible explanation is that there would be a late or slow cyclin degradation mechanism induced by a less efficient pathway, different from that of Cdc15p, and that such partial inactivation of Cdc28p would be sufficient to induce nuclear exit from mitosis but not to polarize actin to the mother–bud neck. Low cAMP levels rescue the cell cycle arrest caused by a cdc15 mutation (Spevak et al., 1993) and therefore alternative pathways for cyclin degradation could rely on intracellular cAMP levels. However, with our current knowledge it is still hard to explain how a failure in the septin ring could influence cAMP-dependent pathways. We studied the nature of the suppression of the cdc15-lyt1 phenotype by overexpressing the gene coding for S. cerevisiae phosphodiesterase, PDE1, and found that it rescued not only the anaphase arrest but also the septation defect (data not shown). Cdc15p might therefore activate morphogenesis in the septum via pathways involving an inactivation of the cAMP-dependent protein kinase.


Morphogenesis beyond cytokinetic arrest in Saccharomyces cerevisiae.

Jiménez J, Cid VJ, Cenamor R, Yuste M, Molero G, Nombela C, Sánchez M - J. Cell Biol. (1998)

Hypotheses for the mechanisms involved in the coordination of morphogenetic events at the end of mitosis. Hypothesis  (a) implies that the Cdc15p-mediated pathway is directly or indirectly involved in B cyclin degradation by the APC and that the  consequent inactivation of the Cdc28p–B cyclin complex accounts for the polarization of the morphogenetic apparatus to the  neck area for septum development. Hypothesis (b) argues that  the Cdc15p pathway, similar to the cdc7 pathway in the fission  yeast, would directly trigger the morphogenetic response for septum formation, perhaps activated by signals derived from  Cdc28p–B cyclin inactivation or coordinated with it via feedback  mechanisms (broken line). The arrest in anaphase observed in  cdc15 and related mutants would be due to a cell cycle checkpoint that would inactivate Cdc28p until morphogenetic events at  the neck are settled. The fact that a septin (cdc10) mutation prevents the delay in budding observed in a cdc15 mutant suggest  that the components of such putative checkpoint rely on the integrity of the septin ring for their functionality.
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Related In: Results  -  Collection

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Figure 9: Hypotheses for the mechanisms involved in the coordination of morphogenetic events at the end of mitosis. Hypothesis (a) implies that the Cdc15p-mediated pathway is directly or indirectly involved in B cyclin degradation by the APC and that the consequent inactivation of the Cdc28p–B cyclin complex accounts for the polarization of the morphogenetic apparatus to the neck area for septum development. Hypothesis (b) argues that the Cdc15p pathway, similar to the cdc7 pathway in the fission yeast, would directly trigger the morphogenetic response for septum formation, perhaps activated by signals derived from Cdc28p–B cyclin inactivation or coordinated with it via feedback mechanisms (broken line). The arrest in anaphase observed in cdc15 and related mutants would be due to a cell cycle checkpoint that would inactivate Cdc28p until morphogenetic events at the neck are settled. The fact that a septin (cdc10) mutation prevents the delay in budding observed in a cdc15 mutant suggest that the components of such putative checkpoint rely on the integrity of the septin ring for their functionality.
Mentions: Lew and Reed (1993) reported that the actin cytoskeleton is not polarized to the septum area to promote cytokinesis until the Cdc28p–Clb2p complex has become dissociated. Here we report that when anaphase arrest persists, a polar budding process is started in the absence of cytokinesis. It could be surmised that the inactivation of the Cdc28p–Clb complex by degradation of B cyclins would be sufficient for the promotion of both nuclear telophase events and cytokinesis and that the Cdc15p pathway would be essential for inactivating the CDK–cyclin complex at this stage. We shall refer to this as the classical hypothesis (Fig. 9 a). Following this interpretation, it is difficult to understand some of our results, such as the overcoming of anaphase arrest in the absence of cytokinesis in cdc15 and, especially, the absence of such an arrest in a double cdc15 cdc10 mutant. A plausible explanation is that there would be a late or slow cyclin degradation mechanism induced by a less efficient pathway, different from that of Cdc15p, and that such partial inactivation of Cdc28p would be sufficient to induce nuclear exit from mitosis but not to polarize actin to the mother–bud neck. Low cAMP levels rescue the cell cycle arrest caused by a cdc15 mutation (Spevak et al., 1993) and therefore alternative pathways for cyclin degradation could rely on intracellular cAMP levels. However, with our current knowledge it is still hard to explain how a failure in the septin ring could influence cAMP-dependent pathways. We studied the nature of the suppression of the cdc15-lyt1 phenotype by overexpressing the gene coding for S. cerevisiae phosphodiesterase, PDE1, and found that it rescued not only the anaphase arrest but also the septation defect (data not shown). Cdc15p might therefore activate morphogenesis in the septum via pathways involving an inactivation of the cAMP-dependent protein kinase.

Bottom Line: This morphogenetic response reflects entry into a new round of the cell cycle: the preference for polarization from the distal pole was lost in bud1 cdc15 double mutants; double cdc15-lyt1 cdc28-4 mutants, defective for START, did not develop apical projections and apical polarization was accompanied by DNA replication.Apical polarization was delayed in cdc15 mutants as compared with budding in control cells and this delay was abolished in a septin mutant.Our results suggest that the delayed M/G1 transition in cdc15 mutants is due to a septin-dependent checkpoint that couples initiation of the cell cycle to the completion of cytokinesis.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Microbiología II, Facultad de Farmacia.

ABSTRACT
The budding yeast lyt1 mutation causes cell lysis. We report here that lyt1 is an allele of cdc15, a gene which encodes a protein kinase that functions late in the cell cycle. Neither cdc15-1 nor cdc15-lyt1 strains are able to septate at 37 degreesC, even though they may manage to rebud. Cells lyse after a shmoo-like projection appears at the distal pole of the daughter cell. Actin polarizes towards the distal pole but the septins remain at the mother-daughter neck. This morphogenetic response reflects entry into a new round of the cell cycle: the preference for polarization from the distal pole was lost in bud1 cdc15 double mutants; double cdc15-lyt1 cdc28-4 mutants, defective for START, did not develop apical projections and apical polarization was accompanied by DNA replication. The same phenomena were caused by mutations in the genes CDC14, DBF2, and TEM1, which are functionally related to CDC15. Apical polarization was delayed in cdc15 mutants as compared with budding in control cells and this delay was abolished in a septin mutant. Our results suggest that the delayed M/G1 transition in cdc15 mutants is due to a septin-dependent checkpoint that couples initiation of the cell cycle to the completion of cytokinesis.

Show MeSH
Related in: MedlinePlus