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Mitotic exit

Mitotic exit is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Mitotic exit rather than just read about it. In short: Mitotic exit is an important transition point that signifies the end of mitosis and the onset of new G1 phase for a cell, and the cell needs to rely on specific control mechanisms to ensure that once it exits mitosis, it never returns to mitosis until it has gone through G1, S, and G2 phases and passed all the necessary checkpoints. Many factors including cyclins, cyclin-dependent kinases (CDKs), ubiquitin ligases…

Mitotic exit — main illustration
Mitotic exit — illustration

Key takeaways

  • Mitotic exit belongs to biology; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Mitotic exit to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Mitotic exit from memory before moving on to harder problems.

Reference excerpt

Mitotic exit is an important transition point that signifies the end of mitosis and the onset of new G1 phase for a cell, and the cell needs to rely on specific control mechanisms to ensure that once it exits mitosis, it never returns to mitosis until it has gone through G1, S, and G2 phases and passed all the necessary checkpoints. Many factors including cyclins, cyclin-dependent kinases (CDKs), ubiquitin ligases, inhibitors of cyclin-dependent kinases, and reversible phosphorylations regulate mitotic exit to ensure that cell cycle events occur in correct order with fewest errors. The end of mitosis is characterized by spindle breakdown, shortened kinetochore microtubules, and pronounced outgrowth of astral (non-kinetochore) microtubules. For a normal eukaryotic cell, mitotic exit is irreversible.

Proteolytic degradation

Many speculations were made with regard to the control mechanisms employed by a cell to promote the irreversibility of mitotic exit in a eukaryotic model organism, the budding yeast Saccharomyces cerevisiae. Proteolytic degradation of cell cycle regulators and corresponding effects on the levels of cyclin-dependent kinases were proposed as a mechanism that promotes eukaryotic cell cycle and metaphase-to-anaphase transition in particular. In this theory, anaphase promoting complex (APC), a class of ubiquitin ligase, facilitates degradation of mitotic cyclins (Clb2) and anaphase-inhibiting factors (PDS1, CUT2) to promote mitotic exit. APC ubiquitinates nine-amino acid motif known as the destruction box (D box) in the NH2-terminal domain of mitotic cyclins for degradation by proteasome. APC in association with Cdc20 (APC-Cdc20) ubiquitinates and targets mitotic cyclins (Clb2) for degradation at initial phase. Simultaneously, APC-Cdc20 mediates degradation of securins, which inhibit separases through binding, at anaphase onset. Released and active separase cleaves cohesin that held sister chromatids together, facilitating separation of sister chromatids and initiates mitotic exit by promoting release of Cdc14 from nucleolus. At later phase, downregulation of Cdk1 and activation of Cdc14, a Cdh1-activating phosphatase, promotes formation of APC in association with Cdh1 (APC-Cdh1) to degrade Clb2s. Cdc20 and Cdh1, which are the activators of APC, recruit substrates such as securin and B-type cyclins(Clb) for ubiquitination. Without Cdk1-Clb2 complexes to phosphorylate proteins that are involved in spindle dynamics such as Sli15, Ase1, and Ask1, spindle elongation and chromosomal segregation are promoted, facilitating mitotic exit. The importance of proteolytic degradation in eukaryotic cell cycle changed the view of cell division as a simple kinase cascade to a more complex process in which interactions among phosphorylation, ubiquitination, and proteolysis are necessary. However, experiments using budding yeast cells with cdc28-as1, an INM-PP1 (ATP analog)-sensitive Cdk allele, proved that destruction of B-type cyclins (Clb) is not necessary for triggering irreversible mitotic exit. Clb2 degradation did shorten the Cdk1-inhibition period required for triggering irreversible mitotic exit indicating that cyclin proteolysis contributes to the dynamic nature of the eukaryotic cell cycle due to slower timescale of its action but is unlikely to be the major determining factor in triggering irreversible cell cycle transitions.

Sic1 levels Discoveries were made which indicated the importance of the level of the inhibitors of cyclin-dependent kinases in regulating eukaryotic cell cycle. In particular, the level of Sic1, a stoichiometric inhibitor of Clb-CDK complexes in budding yeast, was shown to be particularly important in irreversible G1-S transition by irreversibly activating S phase kinases. Sic1 level was shown to play a major role in triggering irreversible mitotic exit (M-G1 transition) as well as in G1-S transition. During mitosis, decreasing levels of Cdk1 leads to the activation of Cdc14, a phosphatase that counteracts Cdk1 via activation of Cdh1 and Swi5, a transcriptional activator of Sic1 proteins. While degradation of Sic1 to a certain low level triggered the onset of S phase, accumulation of Sic1 to a certain high level was required to trigger irreversible mitotic exit. Cdk1-inhibitors could induce mitotic exit even when degradation of B-type cyclins was blocked by expression of non-degradable Clbs or proteasome inhibitors. However, sister chromatids failed to segregate, and cells reverted to mitosis once the inhibitors were washed away, indicating that a threshold level of the inhibitors needs to be achieved to trigger irreversible mitotic exit independently of cyclin degradations. Despite different thresholds of Sic1 level that are required to trigger mitotic exit compared to G1-S transition, the level of Sic1 was shown to play a key role in regulating eukaryotic cell cycle by inhibiting the activity of CDKs.

Dynamical systems approach

… excerpt ends here. Continue reading the full article.

Illustrations

Mitotic exit: Fig. 2 Irreversible and bistable switch in mitotic exit with control parameter being Sic1 level and order parameter being cell cycle phases.
Fig. 2 Irreversible and bistable switch in mitotic exit with control parameter being Sic1 level and order parameter being cell cycle phases.
Mitotic exit: Fig. 3 Simplified network involving Cdk1-Clb2, APC-Cdh1, Sic1, and Cdc14. Double negative feedback loop, mediated by APC-Cdh1 and Sic1, is required to suppress Cdk1-Clb2 and trigger mitotic exit.
Fig. 3 Simplified network involving Cdk1-Clb2, APC-Cdh1, Sic1, and Cdc14. Double negative feedback loop, mediated by APC-Cdh1 and Sic1, is required to suppress Cdk1-Clb2 and trigger mitotic exit.
Mitotic exit: Fig. 4 Flavopiridol induces reversible mitotic exit and cytokinesis if proteasome activity is inhibited.
Fig. 4 Flavopiridol induces reversible mitotic exit and cytokinesis if proteasome activity is inhibited.
Mitotic exit: Fig. 5 Knockdown of Cdc20 induces MOMP and non-MOMP death
Fig. 5 Knockdown of Cdc20 induces MOMP and non-MOMP death
Mitotic exit: Fig. 6 Role of Ste20 in mitotic exit.(D) F-actin of wild-type and Δlte1 cells grown at 14 and 30°C was stained with rhodamine–phalloidin. (E) Serial dilutions of wild-type, Δlte1, Δste20 and Δlte1 Δste20 cells with Gal1-BUB2 were grown for 2 days at 30°C. (F) Δlte1 Δste20 cells have a ME defect. Wild-type, Δlte1, Δste20 and Δlte1 Δste20 cells with Gal1-BUB2 CDC14-GFP grown in YPRA medium were washed and incubated for 3 h at 30°C in YPRA galactose medium to induce Gal1-BUB2 expression. Cells were fixed, stained with DAPI and analysed by fluorescence microscopy. The circles in the cartoon cells indicate the DAPI staining regions. (G) An anaphase Gal1-BUB2 Δlte1 Δste20 CDC14-GFP cell of (F)
Fig. 6 Role of Ste20 in mitotic exit.(D) F-actin of wild-type and Δlte1 cells grown at 14 and 30°C was stained with rhodamine–phalloidin. (E) Serial dilutions of wild-type, Δlte1, Δste20 and Δlte1 Δste20 cells with Gal1-BUB2 were grown for 2 days at 30°C. (F) Δlte1 Δste20 cells have a ME defect. Wild-type, Δlte1, Δste20 and Δlte1 Δste20 cells with Gal1-BUB2 CDC14-GFP grown in YPRA medium were washed and incubated for 3 h at 30°C in YPRA galactose medium to induce Gal1-BUB2 expression. Cells were fixed, stained with DAPI and analysed by fluorescence microscopy. The circles in the cartoon cells indicate the DAPI staining regions. (G) An anaphase Gal1-BUB2 Δlte1 Δste20 CDC14-GFP cell of (F)

Worked examples

Example 1 — a first encounter with Mitotic exit

Start with the simplest possible case. Write down what Mitotic exit claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Mitotic exit before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Mitotic exit ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Mitotic exit

In research
Mitotic exit appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry
Engineering practice reuses Mitotic exit in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom
Mitotic exit is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cell cycle, Mitosis, so understanding it makes those chapters shorter.
In everyday life
Look for Mitotic exit outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.
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How to study Mitotic exit in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Mitotic exit means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Mitotic exit out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Mitotic exit in simple terms?

Mitotic exit is an important transition point that signifies the end of mitosis and the onset of new G1 phase for a cell, and the cell needs to rely on specific control mechanisms to ensure that once it exits mitosis, it never returns to mitosis until it has gone through G1, S, and G2 phases and pa…

Why does Mitotic exit matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Mitotic exit?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Mitotic exit.

Tags

  • Cell cycle
  • Mitosis

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