GO:0010458 exit from mitosis: Cell Cycle Transition, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010458 (exit from mitosis) is the biological process in which a cell leaves M phase and enters a new G1 phase, encompassing the termination of mitosis and cytokinesis.
• Exit from mitosis is driven by the inactivation of CDK1-cyclin B and the activation of the APC/C ubiquitin ligase, which targets cyclin B for degradation.
• Protein phosphatase 2A (PP2A) and Cdc14 are critical effectors that reverse mitotic phosphorylation and allow progression into G1.
• Spatial cues, including spindle position and nuclear partitioning, are coupled to exit from mitosis to ensure genomic integrity.
• The Cdc48/p97 ATPase and Aurora B kinase control chromatin condensation during exit from mitosis, linking mitotic exit to chromatin remodeling.
• Dysregulation of exit from mitosis contributes to aneuploidy and cancer, making its components attractive targets for experimental modeling.
Description
Exit from mitosis (GO:0010458) is the cell cycle transition where a cell leaves M phase and enters a new G1 phase. This process is essential for the proper termination of mitosis and cytokinesis, ensuring that each daughter cell receives a complete and accurate copy of the genome. The transition is tightly regulated by the inactivation of CDK1-cyclin B complexes and the activation of the anaphase-promoting complex/cyclosome (APC/C), which triggers the degradation of cyclin B and other mitotic regulators. Researchers study exit from mitosis to understand how cells coordinate chromosome segregation with cytokinesis and how errors in this process contribute to diseases such as cancer. The process is also coupled to spatial signals, such as spindle position and nuclear partitioning, which ensure that exit from mitosis occurs only after the genome is properly segregated.
exit from mitosis At A Glance
| GO ID | GO:0010458 |
|---|---|
| GO term | exit from mitosis |
| Ontology | biological_process |
| Synonym | exit from mitotic division, mitotic exit |
| Major function | Transition from M phase to G1 phase, involving CDK1 inactivation, APC/C activation, and phosphatase-driven reversal of mitotic phosphorylation |
| Key regulators | APC/C, CDK1-cyclin B, PP2A, Cdc14, Cdc48/p97, Aurora B |
| Spatial coupling | Linked to spindle position and nuclear partitioning |
| Disease relevance | Aneuploidy, cancer, and developmental disorders |
What Is GO:0010458?
GO:0010458 (exit from mitosis) is defined as the cell cycle transition where a cell leaves M phase and enters a new G1 phase. M phase is the part of the mitotic cell cycle during which mitosis and cytokinesis take place. This process involves the coordinated inactivation of mitotic kinases, activation of phosphatases, and degradation of mitotic cyclins, leading to chromosome decondensation, nuclear envelope reformation, and cytokinesis completion.
Why Is exit from mitosis Important in Cell Biology?
Exit from mitosis is a fundamental cell cycle transition that ensures genomic stability by coordinating the end of mitosis with cytokinesis and the onset of G1. Errors in this process can lead to aneuploidy, a hallmark of cancer and developmental disorders. Understanding the molecular mechanisms of exit from mitosis is therefore critical for cancer research, regenerative medicine, and the development of targeted therapies.
• Prevents aneuploidy by ensuring proper chromosome segregation before G1 entry.
• Coordinates cytokinesis with mitotic exit to maintain genome integrity.
• Regulates cell proliferation and differentiation through CDK1 inactivation.
• Involves APC/C, a key ubiquitin ligase frequently dysregulated in cancer.
• Requires PP2A and Cdc14 phosphatases, which are tumor suppressors in some contexts.
• Coupled to spindle position checkpoints that monitor spatial cues.
• Chromatin remodeling during exit from mitosis involves Cdc48/p97 and Aurora B.
• Provides targets for CRISPR-based functional studies in cell cycle research.
• Dysregulation is linked to developmental disorders and neurodegeneration.
• Serves as a model for studying temporal and spatial regulation of cell division.
What Happens During exit from mitosis?
Inactivation of CDK1-Cyclin B
In simple terms: The engine that drives mitosis is turned off.
Exit from mitosis begins with the inactivation of CDK1-cyclin B complexes. This is achieved through the degradation of cyclin B by the APC/C ubiquitin ligase and the inhibitory phosphorylation of CDK1. The inactivation of CDK1 leads to the reversal of mitotic phosphorylation events, allowing cells to exit M phase.
Activation of the APC/C
In simple terms: The cell's recycling machinery is switched on to destroy mitotic proteins.
The anaphase-promoting complex/cyclosome (APC/C) is activated by its co-activator Cdc20 and later Cdh1, targeting cyclin B and securin for proteasomal degradation. This activation is essential for sister chromatid separation and exit from mitosis.
Phosphatase-Driven Reversal of Mitotic Phosphorylation
In simple terms: Enzymes called phosphatases erase the phosphate marks added during mitosis.
Protein phosphatase 2A (PP2A) and the Cdc14 phosphatase reverse CDK1-mediated phosphorylation of mitotic substrates. PP2A regulates entry into and exit from mitosis, while Cdc14 is required for mitotic exit in budding yeast and is regulated by the spindle position checkpoint.
Spatial Coupling to Spindle Position and Nuclear Partitioning
In simple terms: The cell checks that the spindle is in the right place before exiting mitosis.
Exit from mitosis is coupled to spindle position and nuclear partitioning through signaling pathways that monitor the spatial distribution of the spindle and nucleus. In budding yeast, the GTPase signaling pathway controls exit from mitosis in response to spindle position. This ensures that cells do not exit mitosis until the genome is properly segregated.
Chromatin Condensation and Nuclear Envelope Reformation
In simple terms: The chromosomes relax and the nuclear envelope rebuilds.
During exit from mitosis, chromatin decondenses and the nuclear envelope reforms. The Cdc48/p97 ATPase and Aurora B kinase play roles in controlling chromatin condensation during this transition. This step is critical for the re-establishment of the interphase nucleus.
Key Genes Involved in GO:0010458 exit from mitosis
The following genes and proteins are key regulators of exit from mitosis (GO:0010458), based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDK1 | Mitotic kinase; inactivation required for exit from mitosis | Target for cell cycle arrest studies |
| CCNB1 | Cyclin B; degradation by APC/C triggers exit from mitosis | Biomarker in cancer proliferation |
| APC/C | Ubiquitin ligase; targets cyclin B and securin for degradation | Central regulator of mitotic exit |
| CDC20 | APC/C co-activator; activates APC/C during mitosis | Required for anaphase onset and exit |
| CDH1 | APC/C co-activator; maintains APC/C activity in G1 | Regulates late mitotic exit and G1 progression |
| PPP2CA | PP2A catalytic subunit; reverses mitotic phosphorylation | Tumor suppressor role in exit from mitosis |
| CDC14 | Phosphatase; required for mitotic exit in yeast | Model for spatial regulation of exit |
| CDC48 | AAA-ATPase; controls chromatin condensation during exit | Links mitotic exit to chromatin remodeling |
| AURKB | Aurora B kinase; regulates chromatin condensation and cytokinesis | Target in cancer therapy |
| TEM1 | GTPase; regulates exit from mitosis in budding yeast | Noncanonical GTPase signaling |
| LTE1 | GTP exchange factor; activates Tem1 at spindle pole body | Spatial signal for mitotic exit |
| BFA1 | GTPase-activating protein; inhibits Tem1 | Spindle position checkpoint |
| BUB2 | GTPase-activating protein; inhibits Tem1 | Spindle position checkpoint |
| MOB1 | Component of MEN pathway; regulates Cdc14 | Mitotic exit network |
| DBF2 | Kinase; activates Cdc14 in MEN pathway | Regulates exit from mitosis |
| CDC15 | Kinase; upstream of MEN pathway | Spatial regulation of mitotic exit |
| SPO12 | Regulator of Cdc14; promotes mitotic exit | FEAR network component |
How Is exit from mitosis Regulated?
Exit from mitosis is regulated by the APC/C, which is activated by Cdc20 and Cdh1 to degrade cyclin B and securin. CDK1 inactivation is further reinforced by inhibitory phosphorylation and by phosphatases such as PP2A and Cdc14. Spatial signals from the spindle position checkpoint, involving the GTPase Tem1 and its regulators Lte1, Bfa1, and Bub2, ensure that exit from mitosis occurs only after the spindle is correctly positioned. In budding yeast, a noncanonical GTPase signaling mechanism controls exit from mitosis. The Cdc48/p97 ATPase and Aurora B kinase also regulate chromatin condensation during exit.
exit from mitosis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CCNB1 | Cancer (breast, lung) | Knockout or overexpression in cancer cell lines |
| APC/C | Colorectal cancer, aneuploidy | Knockout of APC/C subunits in HCT116 |
| PPP2CA | Developmental disorders, cancer | Point mutation knock-in in HEK293 |
| CDC14 | Cancer, developmental defects | Knockout in yeast and human cells |
| AURKB | Cancer, chromosomal instability | Overexpression in HeLa cells |
Cancer and Aneuploidy
Dysregulation of exit from mitosis leads to aneuploidy, a hallmark of cancer. Overexpression of cyclin B or loss of APC/C function can cause premature or delayed mitotic exit, resulting in chromosomal instability. Targeting CDK1 or APC/C components is a therapeutic strategy in cancers with mitotic defects.
Developmental Disorders
Mutations in genes controlling exit from mitosis, such as PP2A subunits, have been linked to developmental disorders characterized by impaired cell proliferation and differentiation. Proper exit from mitosis is essential for tissue development and homeostasis.
Neurodegeneration
Aberrant cell cycle re-entry, including defects in exit from mitosis, has been implicated in neurodegeneration. Neurons that fail to properly exit mitosis may undergo apoptosis, contributing to neurodegenerative diseases.
From exit from mitosis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does knockout of CDK1 arrest cells in mitosis? | CDK1 knockout cell line (e.g., HCT116) |
| Does point mutation in PPP2CA affect exit from mitosis? | PPP2CA point-mutation knock-in |
| Does overexpression of cyclin B delay mitotic exit? | CCNB1 overexpression in HeLa |
| Does tagging APC/C subunits affect complex assembly? | Tagged knock-in of APC/C subunits |
| Does knockout of CDC14 impair spindle position checkpoint? | CDC14 knockout in budding yeast |
| Does Aurora B inhibition alter chromatin condensation? | AURKB knockout or inhibitor treatment |
How to Study the exit from mitosis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Chromosome segregation and cytokinesis timing | Visualizing exit from mitosis |
| Proteomics | Protein degradation and phosphorylation | Identifying APC/C substrates |
| Phosphoproteomics | Reversal of mitotic phosphorylation | PP2A and Cdc14 targets |
| Flow cytometry | DNA content and cell cycle phase | Confirming G1 entry |
| Yeast genetics | Genetic interactions and spatial cues | Spindle position checkpoint |
| CRISPR knockout | Gene function in mitotic exit | CDK1, APC/C studies |
| RNA-seq | Transcriptional changes during exit | G1 gene expression |
| Immunofluorescence | Protein localization and chromatin state | Aurora B and Cdc48 |
Live-Cell Imaging
Live-cell imaging with fluorescently tagged histones and tubulin allows real-time visualization of chromosome segregation and cytokinesis during exit from mitosis. This method is used to assess the timing and spatial coordination of mitotic exit.
Proteomics and Phosphoproteomics
Mass spectrometry-based proteomics can identify APC/C substrates and phosphorylation changes during exit from mitosis. Phosphoproteomics reveals the reversal of CDK1-mediated phosphorylation by PP2A and Cdc14.
Flow Cytometry
Flow cytometry measures DNA content to confirm exit from mitosis and entry into G1. This method is used to quantify cell cycle progression after genetic perturbations.
Yeast Genetics
Budding yeast is a powerful model for studying exit from mitosis due to conserved pathways and ease of genetic manipulation. Temperature-sensitive mutants and GFP-tagged proteins allow detailed analysis of mitotic exit.
How CRISPR Can Be Used to Study GO:0010458 exit from mitosis
Knockout
CRISPR knockout of genes such as CDK1, CCNB1, or APC/C subunits can be used to study their essential roles in exit from mitosis. Knockout cell lines are valuable for assessing cell cycle arrest and aneuploidy.
Point Mutation
Point mutations in PPP2CA or CDC14 can be introduced using CRISPR to mimic disease-associated variants and study their effects on exit from mitosis. This approach helps dissect phosphatase function in mitotic exit.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) into endogenous loci of APC/C subunits or Aurora B allows real-time tracking of protein dynamics during exit from mitosis. Tagged knock-in models are essential for live-cell imaging.
Overexpression
CRISPR activation or overexpression constructs can drive high-level expression of cyclin B or Aurora B to study their impact on mitotic exit and chromatin condensation. Overexpression models are useful for identifying gain-of-function phenotypes.
How EDITGENE Supports exit from mitosis Research
Researchers studying exit from mitosis-related genes often need to determine whether a candidate gene is causally involved in the transition from M phase to G1. EDITGENE provides a comprehensive suite of CRISPR-based services to enable precise genetic perturbations and functional studies.
Contact EDITGENE today to design your custom CRISPR model for exit from mitosis research.
Frequently Asked Questions About exit from mitosis
What is exit from mitosis (GO:0010458)?
Exit from mitosis is the cell cycle transition where a cell leaves M phase and enters a new G1 phase, involving CDK1 inactivation, APC/C activation, and phosphatase-driven reversal of mitotic phosphorylation.
What genes are involved in exit from mitosis?
Key genes include CDK1, CCNB1, APC/C subunits, CDC20, CDH1, PPP2CA, CDC14, CDC48, AURKB, TEM1, LTE1, BFA1, BUB2, MOB1, DBF2, CDC15, and SPO12.
How is exit from mitosis regulated?
Exit from mitosis is regulated by APC/C-mediated degradation of cyclin B, CDK1 inactivation, and activation of phosphatases PP2A and Cdc14, with spatial cues from the spindle position checkpoint.
Why is exit from mitosis important for cancer?
Dysregulation of exit from mitosis causes aneuploidy and chromosomal instability, which are hallmarks of cancer.
What is the role of APC/C in exit from mitosis?
APC/C is a ubiquitin ligase that targets cyclin B and securin for degradation, triggering exit from mitosis.
How does PP2A regulate exit from mitosis?
PP2A reverses CDK1-mediated phosphorylation of mitotic substrates, promoting exit from mitosis.
What is the spindle position checkpoint?
The spindle position checkpoint monitors spindle orientation and delays exit from mitosis until the spindle is correctly positioned.
What model organisms are used to study exit from mitosis?
Budding yeast is a key model due to conserved pathways and genetic tractability.
What methods are used to study exit from mitosis?
Live-cell imaging, proteomics, phosphoproteomics, flow cytometry, and yeast genetics are commonly used.
How can CRISPR be used to study exit from mitosis?
CRISPR knockout, point mutation, knock-in, and overexpression models enable functional dissection of genes controlling exit from mitosis.
Conclusion
Exit from mitosis (GO:0010458) is a tightly regulated cell cycle transition essential for genomic stability. Its molecular players, including CDK1, APC/C, PP2A, and Cdc14, are conserved and have been extensively studied using yeast genetics, live-cell imaging, and proteomics. Dysregulation of this process contributes to cancer and developmental disorders, making it a critical area for therapeutic targeting. CRISPR-based models offer powerful tools to dissect the mechanisms of exit from mitosis and identify new drug targets.
References
- 1. Hoyt MA. 2000. Exit from mitosis: spindle pole power.. Cell 102(3):267-70 PMID: 10975516
- 2. Morgan DO. 1999. Regulation of the APC and the exit from mitosis.. Nat Cell Biol 1(2):E47-53 PMID: 10559897
- 3. Hunt T. 2013. On the regulation of protein phosphatase 2A and its role in controlling entry into and exit from mitosis.. Adv Biol Regul 53(2):173-8 PMID: 23672858
- 4. Falk JE et al.. 2016. Spatial signals link exit from mitosis to spindle position.. Elife 5 PMID: 27166637
- 5. Zhou X et al.. 2024. A noncanonical GTPase signaling mechanism controls exit from mitosis in budding yeast.. Proc Natl Acad Sci U S A 121(45):e2413873121 PMID: 39475649
- 6. Wolf F et al.. 2007. '... The end of the beginning': cdk1 thresholds and exit from mitosis.. Cell Cycle 6(12):1408-11 PMID: 17581279
- 7. Meyer H et al.. 2010. A role for Cdc48/p97 and Aurora B in controlling chromatin condensation during exit from mitosis.. Biochem Cell Biol 88(1):23-8 PMID: 20130676
- 8. Bardin AJ et al.. 2000. A mechanism for coupling exit from mitosis to partitioning of the nucleus.. Cell 102(1):21-31 PMID: 10929710
