Introductory Cell Biology: Mitosis

Citation: Lee, S. K. (2024, November 16). Introductory Cell Biology: Mitosis. Sepo.

Interphase

During S-phase, DNA polymerase replicates the genome. Replication produces sister chromatids, which are two exact copies of the same chromosome. Each chromatid consists of DNA and its tone proteins (chromatin). During replication, cohesin proteins bind to the genome, forming rings that hold the duplicated sister chromatids together.

Figure 1. Cohesin

During S and G2 phases, the centrosome is replicated. The replicated centrosomes are MTOCs (microtubule organization centers) that nucleate microtubules.

Figure 2. Duplication of Centromeres & the Cell at the end of Interphase

M Phase

M phase can be separated into two big parts (mitosis and cytokinesis).

In mitosis, the duplicated chromosomes are separated precisely and equally by the microtubule-based mitotic spindle. The mitotic spindle is the protein machinery segregating sister chromatids into separate nuclei. It consists of microtubules, motors, and the two centrosomes, the green structures in Figure 3. The spindle assembly checkpoint regulates the mitotic spindle. Two nuclei form as a result of mitosis.

Mitosis is further divided into 5 stages:

• In prophase, the mitotic spindle begins outside the nucleus, chromosomes condense, and the kinetochore assembles.
• In prometaphase, nuclear laminate (intermediate filament proteins) and nuclear pore proteins are phosphorylated. This causes the nuclear envelope to break down into vesicles and the microtubules begin attaching to kinetochores.
• In metaphase, the chromosomes are arranged on the metaphase plate (midway area between the spindle poles). This occurs because of the tension created by the bipolar connection of microtubule-kinetochore attachments.
• In anaphase, the sister chromatids are pulled apart. Two processes occur simultaneously in Anaphase which are called Anaphase A and Anaphase B. In Anaphase A, the chromosomes are pulled poleward. In Anaphase B, the poles are pushed and pulled apart.
• In telophase, nuclear envelopes form around each set of chromosomes to produce two nuclei. Once this happens, cytokinesis is initiated and a contractile ring begins to form if the cell is an animal cell.
• In cytokinesis, the cytoplasm divides into two halves which generates two cells.

Figure 3. Stages of M Phase

Prophase

In prophase, the mitotic spindle begins to form on the outside of the nucleus, kinetochores assemble, and chromosomes condense.

Condensin is similar but not the same as cohesin in that they both form rings. But, condensin organizes chromatin into loops and condenses chromosomes which facilitates segregation during mitosis.

Figure 4. Condensin

Within the mitotic spindle, there are three types of microtubules. These are the astral microtubules, kinetochore microtubules, and interpolar microtubules. Each centrosome acts as a spindle pole and along with their assortment of microtubules, they are collectively called an aster.

Figure 5. The Three Classes of Microtubules Forming the Mitotic Spindle

Prometaphase & Metaphase

The kinetochore connects centromeres to kinetochore microtubules. The centromere is the special region of DNA that is compact and has no protein-coding functions. Therefore, this is where the kinetochore attaches. The kinetochore is the protein complex that connects kinetochore microtubules to the centromere of each chromatid.

Figure 6. Kinetochore Linking Centromeres to Kinetochore Microtubules

Only a stable bipolar microtubule-kinetochore attachment creates the tension needed to arrange the chromosomes at the metaphase plate.

Figure 7. Requirement of Tension for Stable Bipolar Attachment

An unattached kinetochore sends out a signal that prevents the exit of metaphase by preventing the activation of APC/C. If all the kinetochores are attached to the appropriate microtubules, the spindle assembly checkpoint is satisfied and activates the Anaphase Promoting Complex (APC/C). Active APC/C leads to the degradation of M-cyclin and subsequent inactivation of M-Cdk. Active APC/C also leads to the degradation of securin which allows separate to degrade the cohesins holding the chromosomes together. The degradation of cohesins initiates anaphase.

Figure 8. Spindle-assembly Checkpoint

Anaphase

During Anaphase A, chromosomes are pulled poleward. As the kinetochore microtubules are shortened, forces are generated at the kinetochore that move the chromosomes toward their respective spindle pole. The force that pulls the kinetochore toward the pole is the depolymerization at the plus end of the kinetochore microtubules.

Figure 9. Anaphase A

During Anaphase B, the poles are pushed by a sliding force and pulled apart by a pulling force. The sliding force is generated by a kinesin 5 motor protein between interpolar microtubules from opposite poles pushing the poles apart. The pulling force acts directly on the poles to move apart and is facilitated by a dynein motor protein.

Figure 10. Anaphase B

Telophase & Cytokinesis

A contractile ring forms in cytokinesis for animal cells. This contractile ring is actin-based and creates a cleavage furrow.

References

1. Alberts, B., Heald, R., Hopkin, K., Johnson, A., Morgan, D., Roberts, K., & Walter, P. (2023). Essential Cell Biology. W.W. Norton & Company.
2. Graef, M. & Tumbar, T. (Fall 2024 Semester). BIOMG 1350: Introductory Biology: Cell and Developmental Biology. Cornell University.