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The cell cycle

Last updated: February 11, 2021

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The cell cycle is the sequence of events that take place to enable DNA replication and cell division. It can be divided into two phases: interphase and mitosis. Interphase is further divided into the G1 (gap 1), S (synthesis), and G2 (gap 2) phases, which prepare the cell for division. In mitosis, the single cell is dividing into two identical daughter cells. The cell cycle is subject to strict controls that prevent cells with damaged or faulty DNA from further dividing and passing on defects to daughter cells. Controlled cell death (apoptosis) is initiated if the DNA damage is irreparable. Disorders of these regulatory mechanisms play an important role in carcinogenesis.

The mechanisms for apoptosis are discussed in “Cellular changes and adaptive responses:”

Abnormalities of the cell cycle that lead to the development of cancer are discussed in detail in “General oncology.”


G stands for Gap/Growth and S for Synthesis.


G0 phase (resting phase)

  • Definition: a resting phase which a cell enters after exiting the cell cycle from the G1 phase
  • Duration: variable
  • Characteristics
    • Cells that enter the G0 phase are differentiated, have specific functions, and are no longer undergoing cell division.
    • Most mature tissue cells are in the G0 phase.
    • Certain cell types reenter the G1 phase after the G0 phase when exposed to certain stimuli (e.g., hepatocyte proliferation after hepatectomy).

Most cells in mature tissue are in the resting phase (G0 phase). Mitosis is rare in mature differentiated tissue.

One of the features of malignant tumors is the high mitotic rate and dedifferentiation of tumor cells (i.e., reversal to less differentiated cells with a high mitotic rate). Multiple mitotic figures seen on microscopy are indicative of a malignant process.

M phase

  • Definition: the process of cell division from the distribution of DNA to the budding of a cellular body
  • Duration: ∼1 h (shortest phase of the cell cycle)


  • Definition: the final phase of the cell cycle, following the replication of DNA
  • 5 phases of mitosis
    1. Prophase
      • Chromosome condensation
      • Centrosome separation: The centrosome is the point of origin of the mitotic spindle. It consists of two centrioles and a surrounding matrix, from which the microtubules emerge.
      • Formation of the mitotic spindle
    2. Prometaphase
    3. Metaphase: maximal condensation of the chromosomes, which are aligned along the equatorial plane of the cell
    4. Anaphase
    5. Telophase
  • Mitotic index: the ratio of the number of cells undergoing mitosis to the total number of cells in the given population (e.g., per 1,000 cells or per microscopic area in the specimen)

Proper functioning of the mitotic spindle is a prerequisite for chromosome transportation. Inhibition with spindle poisons leads to arrest of mitosis and cessation of cell division. Spindle poisons include colchicine, which inhibits microtubule polymerization, as well as vinca alkaloids and taxanes.


Basic principles of cell cycle regulation

The p53 tumor suppressor prevents cells with genetic errors from entering the S phase of the cell cycle.

Mutations in tumor suppressor genes result in uncontrolled proliferation. An important example is Li-Fraumeni syndrome, resulting from a mutation in the p53 tumor suppressor gene.

Important checkpoints and transition points

  • Definition: : A cell cycle checkpoint is a specific point in time that marks the transition from one cell cycle phase to another during which the current condition of a cell is revised (i.e., if all requirements for the transition to the next phase are met)
    • If DNA is faulty or damaged, the cell cycle can be stopped in order to repair the DNA.
    • Apoptosis is initiated if the DNA damage is not repaired.

G1 checkpoint

Mutations in the Rb gene lead to the dysregulation of the cell cycle and, thus, unrestrained growth of retinal tumor cells (e.g., retinoblastoma).

G2 checkpoint

M checkpoint (spindle checkpoint)

Cell types

Cell types by replication properties
Types Characteristics Examples
Labile cells
  • Rapidly dividing cells
  • Have a short G1 phase and never enter the G0 phase
  • Fast cell turnover makes these cells specifically vulnerable to chemotherapy.
Quiescent (stable) cells
Permanent cells