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Fungal Cell Cycle: A Unicellular versus Multicellular Comparison

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  • Authors: Ilkay Dörter1, Michelle Momany2
  • Editors: Joseph Heitman3, Eva Holtgrewe Stukenbrock4
    Affiliations: 1: Fungal Biology Group and Plant Biology Department, University of Georgia, Athens, GA 30602; 2: Fungal Biology Group and Plant Biology Department, University of Georgia, Athens, GA 30602; 3: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; 4: Environmental Genomics, Christian-Albrechts University of Kiel, Kiel, Germany, and Max Planck Institute for Evolutionary Biology, Plön, Germany
  • Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
  • Received 03 August 2016 Accepted 24 September 2016 Published 09 December 2016
  • Michelle Momany, [email protected]
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  • Abstract:

    All cells must accurately replicate DNA and partition it to daughter cells. The basic cell cycle machinery is highly conserved among eukaryotes. Most of the mechanisms that control the cell cycle were worked out in fungal cells, taking advantage of their powerful genetics and rapid duplication times. Here we describe the cell cycles of the unicellular budding yeast and the multicellular filamentous fungus . We compare and contrast morphological landmarks of G1, S, G2, and M phases, molecular mechanisms that drive cell cycle progression, and checkpoints in these model unicellular and multicellular fungal systems.

  • Citation: Dörter I, Momany M. 2016. Fungal Cell Cycle: A Unicellular versus Multicellular Comparison. Microbiol Spectrum 4(6):FUNK-0025-2016. doi:10.1128/microbiolspec.FUNK-0025-2016.


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All cells must accurately replicate DNA and partition it to daughter cells. The basic cell cycle machinery is highly conserved among eukaryotes. Most of the mechanisms that control the cell cycle were worked out in fungal cells, taking advantage of their powerful genetics and rapid duplication times. Here we describe the cell cycles of the unicellular budding yeast and the multicellular filamentous fungus . We compare and contrast morphological landmarks of G1, S, G2, and M phases, molecular mechanisms that drive cell cycle progression, and checkpoints in these model unicellular and multicellular fungal systems.

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Mitosis, septation, and cytokinesis in and . Three rounds of mitosis in beginning from vegetatively growing yeast cell (top) compared to beginning from dormant conidium (bottom). Black dots are nuclei. M1, M2, and M3 denote the indicated mitotic divisions.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Cell cycle landmarks in and . Major morphological landmarks for each cell cycle stage are shown for (left) and (right). Gray circle, nucleus; solid border, intact nuclear envelope; broken-line border, partial nuclear pore complex disassembly; small black dots, spindle pole bodies; blue dots, nucleolus; lines, microtubules. (Data from references 117 and 120 .)

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Cyclin-dependent kinase (CDK)/cyclin B regulation. Comparison of CDK and cyclin activity at G2/M phases in (canonical), , and . (Data from reference 52 .)

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Model of the Cdc fourteen early anaphase release (FEAR) network and mitotic exit network (MEN) at the end of mitosis. In early anaphase in the FEAR network promotes the release of Cdc14 from the nucleolus. In late anaphase the MEN releases Cdc14 from the nucleus into the cytoplasm, where it activates both Swi5 and Hct1. Swi5 triggers the transcription of the cyclin-dependent kinase (CDK) inhibitor Sic1. Hct1 binds the anaphase-promoting complex (APC), and this complex marks Cdk1 for degradation. These events cause the cell to exit mitosis and enter into a new cell division cycle. Gray circles represent the nucleus. (Modified from reference 121 with permission.)

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Cell cycle checkpoints in and . Sensors (depicted as rectangles) monitor the completion of specific cell cycle events (depicted as diamonds) and forward the information to effectors that halt or reboot the cell cycle. G1: Reboot regulation (not reported in ). S phase: DNA damage network includes branches that are responsible for DNA repair and damage-induced transcription. Depending on when the checkpoint is triggered, cell cycle progression can be delayed or halted at G1/S or G2/M boundaries or DNA replication can be slowed (shown as dotted line). S/G2: Morphogenesis checkpoint (not reported in ). M phase: Spindle assembly checkpoint (SAC) and spindle position checkpoint (SPOC) SAC arrests at metaphase, preventing anaphase. SPOC not reported in . (Data from reference 122 .)

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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DNA damage checkpoint in and . Sensor proteins monitor DNA damage and transmit the information to transducers and effectors that ultimately modulate the cell cycle. Only proteins discussed in text are shown. DSB, double-strand break; RPA, replication protein A; ATRIP, ATR interacting protein. (Data from reference 80 .)

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Spindle assembly checkpoint (SAC) in . Unattached kinetochores activate the SAC response by recruiting MPS1, which phosphorylates Knl1. The KMN (Knl1-Mis12-Ndc80) network serves as a scaffold for the recruitment of checkpoint proteins. Binding of Bub1/3 promotes the recruitment of the Mad1/Mad2 core complex. Kinetochore-bound Mad1/Mad2 catalyzes the conformational change of the open Mad2-O to the closed Mad2-C form. Mad2-C interacts with Cdc20 and forms the mitotic checkpoint complex (MCC) consisting of Cdc20, Mad2-C, BubR1, and Bub3. This inhibits the anaphase-promoting complex activator Cdc20 and blocks the metaphase to anaphase transition. KT, kinetochore. (Data from reference 92 .)

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Spindle position checkpoint (SPOC) controls mitotic exit in . When the spindle is misaligned, Bub2/Bfa1 keeps Tem1 in its inactive form. Kin4 protects Bub2/Bfa1 itself from an inhibitory modification. Bub2/Bfa1 disappears from the mother cell once one spindle pole body (SPB) is correctly positioned in the daughter cell. At the same time the amount of Tem1 and Bub2/Bfa1 increases at the SPB of the daughter cell. Lte1, which is located at the cortex of the daughter cell, activates Tem1, and Bub2/Bfa1 is phosphorylated by the polo kinase Cdc5. Bub2/Bfa1 disappears from the daughter cell, whereas Kin4 is removed from the SPB of the mother cell. Simultaneously, Lte1 diffuses into the cytoplasm of the mother and daughter cells. It is possible that all these events contribute equally to the activation of the mitotic exit network. The nucleus is depicted as a gray circle, and the pink highlighted part of the cell shows Lte1 in the cytoplasm. The blue empty circle represents the GTPase Tem1, and the blue filled circle is Tem1 associated with the dimer complex Bub2/Bfa1. (Data from reference 123 .)

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Summary of the morphogenesis checkpoint in . In the nucleus the kinase Swe1 inhibits Cdc28 via phosphorylation. When the bud emerges, Elm1, Hsl1, and Hsl7 are recruited to the bud side of the septin collar and in turn recruit a subpopulation of Swe1 from the nucleus to the bud side of the septin collar, where it is degraded. This depletes nuclear Swe1 and allows progression into mitosis. Actin depolymerization and delayed budding activate the morphogenesis checkpoint, which stabilizes Swe1. Dotted lines represent the septin collar between mother and bud. The gray circle represents the nucleus. Swe1 with a solid border is stable and active. Swe1 with a broken line border is destabilized. The arrow shows recruitment of Swe1 from the nucleus.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016
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Cell cycle proteins discussed in text

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.FUNK-0025-2016

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