1.1 Cell cycle

The cell cycle is the ordered series of events by which a eukaryotic cell grows, copies its DNA and divides into two daughter cells. It is made up of interphase, when the cell grows and replicates its chromosomes, and the mitotic (M) phase, when the nucleus and then the cytoplasm divide. The cycle is tightly controlled at checkpoints, and loss of that control is the root cause of cancer. For an applied biology technologist, the cell cycle explains why root tips and bone marrow are used to study dividing cells, why some drugs target dividing cells, and why abnormal cell counts appear in cytology slides. Example: a cytology laboratory at a sub-county hospital in Ahero screens cervical smears for cells showing abnormal nuclei, a sign of cells that have escaped normal cell cycle control.

Phases of the cell cycle

A typical somatic cell spends about 90% of its cycle in interphase. In a human cell growing in culture, one full cycle takes roughly 24 hours, of which mitosis takes only about one hour.

• G1 phase (first gap): The cell grows, makes proteins and organelles, and carries out its normal functions. The cell "decides" at the end of G1 whether to divide. It has the diploid DNA content, written 2C.
• S phase (synthesis): DNA is replicated so that each chromosome becomes two identical sister chromatids joined at the centromere. DNA content doubles from 2C to 4C, but the chromosome number stays the same (46 in humans). Centrosomes are also duplicated in animal cells.
• G2 phase (second gap): The cell continues to grow, makes the proteins needed for division (such as tubulin for the spindle) and checks that DNA replication is complete and error free.
• M phase (mitotic phase): Mitosis (division of the nucleus) followed by cytokinesis (division of the cytoplasm) produces two genetically identical daughter cells.
• G0 phase (resting phase): Cells that stop dividing leave the cycle from G1 and enter G0. Mature neurones and skeletal muscle cells stay in G0 permanently; liver cells stay in G0 but can re-enter the cycle after injury.

Control of the cell cycle

The cycle is driven by proteins called cyclins and cyclin-dependent kinases (CDKs). A CDK is active only when bound to its cyclin, and cyclin levels rise and fall at set points in the cycle. The active cyclin-CDK complexes add phosphate groups to target proteins that push the cell into the next phase.

• G1 checkpoint (restriction point): Checks cell size, nutrients, growth factor signals and DNA damage. The protein p53 halts the cycle if DNA is damaged, allowing repair or triggering programmed cell death (apoptosis).
• G2/M checkpoint: Checks that DNA has been fully and correctly replicated before mitosis begins.
• Metaphase (spindle) checkpoint: Checks that every chromosome is attached to spindle fibres from both poles before anaphase starts, preventing unequal sharing of chromosomes.
• Growth factors: External signals such as platelet-derived growth factor stimulate cells to pass the G1 checkpoint, for example during wound healing.
• Contact inhibition: Normal cells stop dividing when they touch neighbouring cells, which keeps tissues at the right size.

Cell cycle and cancer

Cancer develops when mutations in the genes that control the cycle let cells divide without restraint. Proto-oncogenes normally promote division; when mutated they become oncogenes that act like a stuck accelerator. Tumour suppressor genes such as p53 normally stop division; when both copies are lost, the brake fails. The result is a mass of cells (tumour) that may invade nearby tissue and spread (metastasis).

• Chemotherapy: Drugs such as vincristine block spindle formation and stop cells in metaphase, while others interfere with DNA replication in S phase.
• Radiotherapy: Ionising radiation damages DNA so badly that rapidly dividing cancer cells die.
• Side effects: Normal fast-dividing cells (hair follicles, gut lining, bone marrow) are also affected, which explains hair loss and low blood counts during treatment.
• Screening: Cytology tests such as the Pap smear detect abnormal cells early, before invasive cancer forms.
• Risk factors: Tobacco smoke, aflatoxin in poorly stored maize, human papilloma virus and ionising radiation all damage DNA or disturb cycle control.

Measuring cell cycle activity in the laboratory

The proportion of cells in division in a tissue is expressed as the mitotic index.

Mitotic index = number of cells in mitosis ÷ total number of cells counted × 100

Example calculation: in an onion root tip squash, 36 of 400 cells counted are in a stage of mitosis.

Mitotic index = 36 ÷ 400 × 100

Mitotic index = 0.09 × 100

Mitotic index = 9%

A high mitotic index shows a rapidly growing tissue, such as a root tip meristem or a tumour.