Mitosis is the process by which duplicated chromosomes are divided between the two daughter cells, thus transmitting genetic information to the next cell cycle. Mitosis comprises nuclear division (karyokinesis), which is followed by cytoplasmic division (cytokinesis), together forming the mitotic (M) phase of the cell cycle. Mitosis is a dynamic process that mechanically segregates chromosomes using the spindle apparatus, a microtubule (MT)‐based structure. Mitotic events, such as chromosome condensation, nuclear envelope breakdown, spindle assembly, chromosome alignment, chromosome segregation, nuclear envelope reformation, chromosome decondensation and cytokinesis must occur in a precise order. This is governed by the protein phosphorylation by cyclin‐dependent kinase (CDK) 1 and other mitotic kinases, and also ubiquitylation by the anaphase‐promoting complex/cyclosome (APC/C). For high‐fidelity chromosome segregation, proper attachment of microtubules to kinetochores is ensured by numbers of mechanisms. Failure in these mechanisms results in cell death or aneuploidy; the latter often leads to oncogenesis and cancer progression.

Key Concepts

  • CDK1 (cyclin‐dependent kinase 1) activity drives mitotic progression.
  • Spindle bipolarity is maintained by the balance of forces acting on microtubules.
  • Centrosomes act as spindle poles, but spindles can be formed without centrosomes.
  • Proper attachment of microtubules to kinetochores is essential for faithful chromosome segregation.
  • Spindle‐assembly checkpoint (SAC) ensures the proper attachment of kinetochores to microtubules for all the chromosomes.
  • APC/C (anaphase‐promoting complex/cyclosome) triggers chromosome segregation and mitotic exit. Most cancer cells show aneuploidy, which is mainly caused by chromosomal instability.

Keywords: chromosome segregation; spindle; microtubule; cytokinesis; centromere; kinetochore; centrosome; cyclin‐dependent kinase; phosphorylation; proteolysis

Figure 1. Stages of M phase in animal cells (a) Live cell imaging of dividing human cells in culture. Human cervical carcinoma cells (HeLa) expressing EGFP‐α‐tubulin, EGFP‐CENP‐A and H2B‐mCherry, which visualise microtubules (green), kinetochores (green) and chromosomes (red), respectively, were imaged every minute. Representative images for different phases of cell division are shown. (b) Schematic diagrams showing different phases of cell division. Red arrows show directions of chromosome motion or force acting on chromosomes.
Figure 2. Phases and regulation of M phase. (a) The cell division cycle. The durations of individual phases depend on the organism and cell type and are therefore not drawn to scale. (b) A simplified model of the major controls over entry into, and exit from, mitosis in mammalian cells, highlighting the role of a phosphatase, CDC25, in regulating the onset of mitosis, and that of a ubiquitin ligase, the anaphase‐promoting complex/cyclosome (APC/C), in controlling the exit from mitosis. Both CDC25 and the APC/C are targets of checkpoint mechanisms that stop cell‐cycle progression until conditions are appropriate for cells to divide. CDK, cyclin‐dependent kinase.
Figure 3. A metaphase spindle. This simplified representation illustrates the distribution of three distinct types of spindle microtubules (astral MTs, polar MTs and kinetochore MTs) relative to centrosomes, chromosomes and cell cortex (plasma membrane).
Figure 4. Kinetochore–microtubule (MT) attachments. (a) Forms of kinetochore–MT attachments. Bipolar, or amphitelic, attachment is the proper attachment where sister kinetochores attach to MTs from opposite spindle poles and tension is exerted between them. Monotelic attachment is the attachment of only one of the sister kinetochores to MTs. Syntelic attachment is the attachment of both kinetochores to MTs from the same spindle pole, and there is no tension between kinetochores. Merotelic attachment is the attachment of MTs from both spindle poles to a single kinetochore. (b) Structure of a kinetochore. (Left) On kinetochores in mammalian cells forming bipolar attachment, 20–30 MTs are attached and called a K‐fibre. (Right) For each MT in a K‐fibre, multiple copies of the Ndc80 complex bind to its lateral surface and tether the kinetochore to the MT end. (c) Regulation of kinetochore–MT attachment. Phosphorylation of Ndc80, a component of the Ndc80 complex, by Aurora B reduces the affinity of the Ndc80 complex to MTs, allowing release of MTs from kinetochores. In contrast, dephosphorylation of Ndc80 by PP1 and PP2A increases the affinity of the Ndc80 complex to MTs and thus stabilises the kinetochore–MT attachment.
Figure 5. Spindle assembly checkpoint (SAC) and the regulation of anaphase onset and mitotic exit by the APC/C. In prometaphase, components of the SAC localise to kinetochores that do not attach to MTs or that are not under tension, and catalyse conformational change of Mad2. The Mad2 species subjected to the conformational change plays a role in inhibiting the activation of the APC/C complexed with Cdc20. When all the kinetochores form bipolar attachment to MTs in metaphase, components of the SAC are no longer on kinetochores, thus conformational change of Mad2 ceases, allowing the activation of APC/C‐Cdc20. APC/C‐Cdc20 polyubiquitinates securin and targets it for degradation, which activates separase. Activated separase then cleaves cohesin, triggering sister chromatid separation and anaphase onset. In addition, APC/C‐Cdc20 polyubiquitinates cyclin B and targets it for degradation, which downregulates CDK1 activity and leads to mitotic exit. Ub, ubiquitin.


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Tanaka, Kozo(Jul 2015) Mitosis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001356.pub2]