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#mitotic exit

6 public questions tagged with this topic.

Cell Cycle Regulation

The APC/C-Cdh1 complex is required for:

Specificity and timing of APC/C activity arise from sequential association with two adaptors, Cdc20 and Cdh1, both containing seven WD40 repeats forming beta-propeller that binds D-box and KEN motifs. During prometaphase and metaphase, APC/C-Cdc20 polyubiquitinates securin and cyclin B to trigger anaphase and mitotic exit. At telophase, cyclin B degradation reduces CDK1 activity, allowing Cdc14 phosphatase to dephosphorylate Cdh1, enabling its binding to APC/C core. APC/C-Cdh1 then operates from late mitosis through entire G1, continuously ubiquitinating mitotic cyclins A and B, mitotic kinase

Ref: Peters, Nature Reviews Mol Cell Biol 2006, APC/C Mechanisms. Alberts 7th ed., Chapter 17.

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Cell Cycle Regulation

Which factor regulates the exit from mitosis?

Finishing mitosis demands comprehensive reversal of CDK1 mediated phosphorylations and elimination of cyclin B activity. Cdc14 family phosphatases coordinate this program. In budding yeast, Cdc14 resides sequestered in nucleolus bound to inhibitor Net1 also called Cfi1. Mitotic entry maintains sequestration via high CDK activity. In early anaphase, FEAR pathway comprising separase, Slk19 homodimer, Spo12, Zds1 and Zds2 induces transient release. Subsequently Mitotic Exit Network MEN, Hippo-like cascade of Tem1 GTPase localized at daughter spindle pole body, polo kinase Cdc15 and Dbf2-Mob1 comp

Ref: Stegmeier & Amon, Closing Mitosis: Regulation of Cdc14 Phosphatase, Annu Rev Genet 2004; Bardin & Amon, MEN and Mitotic Exit.

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Cell Cycle Regulation

Which of the following prevents mitotic exit if chromosomes are not properly aligned?

Accurate mitosis demands anaphase initiation strictly after all chromosomes achieve stable amphitelic attachment generating tension. The spindle assembly checkpoint monitors this criterion. Unattached kinetochores catalyze assembly of Mitotic Checkpoint Complex composed of Mad2 locked as C-Mad2, BubR1 ortholog of yeast Mad3, Bub3 and Cdc20 coactivator of APC/C. Within MCC, BubR1 provides pseudosubstrate motif inserting KEN boxes into Cdc20 binding pockets plus direct inhibition of APC/C central cavity, thereby preventing ubiquitination of securin and cyclin B. BubR1 also functions as protein k

Ref: Musacchio, Spindle Assembly Checkpoint Structure of BubR1-MCC, Curr Biol 2015; NCBI Bookshelf, SAC component BubR1.

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Cell Cycle Regulation

Which protein deactivates mitotic CDKs during mitotic exit?

Mitotic exit requires not only destruction of cyclin B but comprehensive reversal of CDK1-Cyclin B phosphorylation on hundreds of substrates. Specialized phosphatases execute this program. In budding yeast, Cdc14 is the master phosphatase. Most of the cell cycle it is sequestered in nucleolus bound to inhibitor Net1 or Cfi1. Two release pathways operate sequentially: the Cdc Fourteen Early Anaphase Release pathway involving separase, Slk19, Spo12 and Zds1/Zds2 provides transient liberation in early anaphase, while the Mitotic Exit Network composed of Tem1, Cdc15 and Dbf2-Mob1 kinases sustains

Ref: Stegmeier & Amon, Closing Mitosis: Role of Cdc14 Phosphatases, Annu Rev Genet 2004; Alberts et al., Chapter 17, Mitotic Exit Control.

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Cell Cycle Regulation

Which protein inhibits Tem1 to prevent premature mitotic exit?

Exit from mitosis in Saccharomyces cerevisiae is governed by the Mitotic Exit Network, a conserved Hippo-like kinase cascade initiated by small GTPase Tem1 at spindle pole bodies. Inaccurate spindle positioning would generate anucleate daughters if MEN fired prematurely. The Spindle Position Checkpoint prevents this error. Kin4 kinase, enriched at mother cell cortex and mother spindle pole body, acts as central checkpoint effector. When anaphase spindle fails to penetrate the bud neck, Kin4 phosphorylates Bfa1 subunit of the Bfa1-Bub2 GTPase activating complex. Phosphorylated Bfa1-Bub2 remains

Ref: Bardin & Amon, Molecular Cell Biology of Spindle Position Checkpoint, Nat Rev Mol Cell Biol 2001; NCBI Bookshelf, MEN and SPOC signaling.

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Cell Cycle Regulation

Which of the following prevents premature mitotic exit?

In budding yeast, mitotic exit is controlled by mitotic exit network, abbreviated MEN, culminating in release of phosphatase Cdc14 from nucleolus to dephosphorylate CDK substrates and activate APC/C-Cdh1 and Sic1 to drive G1 entry. Premature exit would cause cytokinesis before chromosome segregation, generating aneuploid progeny. Two mechanisms prevent this: inhibition of upstream GTPase Tem1 keeps MEN inactive until anaphase when Tem1 is recruited to spindle pole body and activated by Lte1, ensuring that only elongated spindles trigger exit. Separately, Cdh1, alternative activator of APC/C, i

Ref: Visintin et al., Mol Cell 1998, Mitotic Exit Network; Stegmeier & Amon, Ann Rev Genet 2004, Closing Mitosis.

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