Prophase: Preparation of the Genetic Apparatus
The first and most event-ful stage is prophase. The primary task of the cell at this stage is the compaction of genetic material. Under the influence of MPF (mitosis-promoting factor), the protein complex condensin is activated.
Chromatin folding occurs in a strict sequence:
- Nucleosomal level (initial euchromatin).
- Superspiral level (chromatin fiber).
- Loop level, where rosettes form and the chromonema is established.
- Chromatid level (fully condensed structure).
By the end of the phase, chromosomes consist of two sister chromatids held together by cohesins. This heavy DNA packaging makes enzyme activity impossible: transcription stops completely, rRNA genes are inactivated, and nucleoli disappear from the nucleus.
Membrane Breakdown and Spindle Formation
Concurrently in prophase, MPF phosphorylates nuclear lamina proteins. This leads to the depolymerization of the inner nuclear structural framework, causing the nuclear envelope to break down into microvesicles. The endoplasmic reticulum and Golgi apparatus also fragment. The biological purpose of this breakdown is to remove mechanical obstacles to chromosome movement and prevent extraneous membranes from entering the future nuclei.
Simultaneously, diplosomes (centrioles duplicated during the S-phase) migrate to opposite poles. Microtubules polymerize from previously prepared tubulin protein, forming the mitotic spindle apparatus.
Metaphase and Spindle Architecture
In metaphase, the nuclear envelope is absent, and chromosomes reach peak condensation. They align along the equatorial plane, forming the metaphase plate. At this point, cohesins persist exclusively at the centromeric regions. Functionally, the cell carries a tetraploid set of single-chromatid chromosomes.
Spindle microtubules are divided into three functional types:
- Kinetochore microtubules — link the pole to the kinetochore at the centromere of the chromosome.
- Polar microtubules — extend toward the center and overlap with microtubules from the opposite pole.
- Astral microtubules — anchor the poles by abutting the cell cortex.
Anaphase: Molecular Trigger and Chromosome Segregation
The transition to anaphase is triggered by the APC (anaphase-promoting complex), which is activated by MPF. The APC tags cohesins with a marker protein, ubiquitin. Tagged cohesins are rapidly cleaved in proteasomes. The loss of connection between chromatids initiates their movement.
Chromosomes move toward opposite poles centromere-first. This movement is driven by the shortening of kinetochore microtubules, the elongation of polar microtubules, and the action of specialized motor proteins. At the end of anaphase, the APC tags MPF itself, and its degradation serves as a signal to transition to the next stage.
Telophase and Cytokinesis
In telophase, protein phosphatases dominate, reversing the effects of MPF. Chromosomes decondense. Membrane vesicles bind to chromosomes, forming isolated mini-nuclei called karyomeres. Following the insertion of nuclear pores and lamin proteins, karyomeres of a single pole fuse into a unified daughter nucleus. -In late telophase, cytokinesis occurs. An actomyosin ring assembles at the cell equator, constricting the plasma membrane and dividing the cytoplasm. Only after successful division do the ER and Golgi membranes reassemble in the daughter cells.
Cell Cycle Control and Pathology
Division fidelity is monitored at specific checkpoints in G1, S, G2, and metaphase. The system checks DNA integrity (absence of double-strand breaks), spindle assembly, and proper previous segregation. If a flaw is detected, the cycle halts for repair, or apoptosis is triggered if defects are irreparable.
Failures in the control system lead to tumorigenesis (in somatic tissues) or embryonic abnormalities. If mitosis occurs without cytokinesis, multinucleated cells form. If both nuclear and cytoplasmic division fail (e.g., via endoreduplication), polyploid cells with excess chromosome sets arise.