Mitosis and cytokinesis
Also known as: prophase, prometaphase, metaphase, anaphase, telophase, cytokinesis, mitotic spindle, kinetochore, cleavage furrow
Division of the replicated nucleus into two genetically identical nuclei in five phases — prophase, prometaphase, metaphase, anaphase and telophase — followed by cytokinesis, the division of the cytoplasm.
Overview
Prophase: replicated chromatin condenses (condensins) into visible chromosomes, each of two sister chromatids held together by cohesin; the nucleolus disperses; the two centrosomes move apart and nucleate the mitotic spindle. Prometaphase: CDK1 phosphorylates lamins and nucleoporins and the nuclear envelope breaks down; spindle microtubules "search and capture" chromosomes at their kinetochores (protein complexes on the centromeres). Metaphase: chromosomes are pulled back and forth until they align at the metaphase plate (equatorial plane), with sister kinetochores attached to opposite poles (bi-orientation). The spindle-assembly checkpoint waits until every kinetochore is attached.
Anaphase: APC/C–Cdc20 ubiquitinates securin (and cyclin B) for proteasomal destruction; freed separase cleaves cohesin and the sister chromatids separate abruptly — now called daughter chromosomes. In anaphase A they move toward the poles as kinetochore microtubules shorten; in anaphase B the poles move apart as overlapping polar microtubules slide (kinesin-5) and astral microtubules are pulled by cortical dynein. Telophase: chromosomes arrive at the poles and decondense; the nuclear envelope re-forms around each set; nucleoli reappear.
Cytokinesis usually begins in late anaphase: a contractile ring of actin and myosin II assembles beneath the plasma membrane at the former metaphase plate (positioned by the spindle midzone) and constricts, forming a cleavage furrow that pinches the cell into two; the final bridge (midbody) is cut by ESCRT proteins. Mitosis takes about an hour.
Parts & subdivisions
- ProphaseChromosome condensation, spindle formation, nucleolus disappears.
- PrometaphaseNuclear envelope breakdown; kinetochore capture.
- MetaphaseChromosomes aligned at the metaphase plate; spindle checkpoint.
- AnaphaseCohesin cleaved; chromatids pulled to opposite poles (A) and poles separate (B).
- TelophaseNuclear envelopes and nucleoli re-form; chromosomes decondense.
- CytokinesisActin–myosin contractile ring forms the cleavage furrow.
- Kinetochore, polar (interpolar) and astral microtubules from two centrosomes.
Anatomy
- Histology
Mitotic figures are counted (the mitotic index) to grade tumours and assess proliferation; atypical (e.g. tripolar) mitoses suggest malignancy. Ki-67 immunostaining marks all cycling (non-G0) cells.
Function
- Growth of the organism.
- Renewal of labile tissues and repair after injury.
- Asexual reproduction of somatic cells with an identical diploid genome.
Clinical significance
Antimitotic drugs
Vinca alkaloids (block tubulin polymerisation) and taxanes (stabilise microtubules) prevent normal spindle function, triggering the spindle checkpoint and apoptosis. Colchicine is used in the laboratory to arrest cells in metaphase for karyotyping.
Mitotic nondisjunction
Errors after fertilisation produce mosaicism (two cell lines, e.g. mosaic Down or Turner syndrome), usually with milder phenotypes.
Mnemonics
Phases
"I Picked My Apples Today" — Interphase, Prophase (+ Prometaphase), Metaphase, Anaphase, Telophase. Metaphase = Middle; Anaphase = Apart; Telophase = Two nuclei.
Test yourself
Crossing over between non-sister chromatids of homologous chromosomes occurs during:
- Prophase I (pachytene)
- Metaphase I
- Anaphase II
- S phase
Answer: Prophase I (pachytene)
Homologues synapse via the synaptonemal complex (zygotene) and exchange segments in pachytene; the crossover sites become visible as chiasmata in diplotene.
What directly triggers the separation of sister chromatids at anaphase?
- Phosphorylation of lamins by CDK1
- Cleavage of cohesin by separase after APC/C-mediated destruction of securin
- Depolymerisation of the contractile actin ring
- Activation of caspase-3
Answer: Cleavage of cohesin by separase after APC/C-mediated destruction of securin
Once every kinetochore is attached, the spindle-assembly checkpoint releases APC/C–Cdc20, which ubiquitinates securin (and cyclin B) for proteasomal destruction. Freed separase cleaves cohesin and chromatids separate.
Paclitaxel (a taxane) kills dividing cancer cells by:
- Preventing tubulin polymerisation
- Stabilising microtubules so the mitotic spindle cannot function
- Inhibiting actin polymerisation
- Inhibiting topoisomerase II
Answer: Stabilising microtubules so the mitotic spindle cannot function
Taxanes hyperstabilise microtubules; vinca alkaloids (vincristine, vinblastine) and colchicine instead inhibit polymerisation. Both arrest cells in M phase.
Compiled from standard anatomy and physiology references — see the Cells & Tissues sources. For education only; not medical advice.