CorpusHuman Anatomy
Cells & TissuesCell process

Cell cycle

Also known as: interphase, G1 phase, S phase, G2 phase, G0, checkpoints, cyclins, CDK, p53, Rb, restriction point

The ordered sequence of growth, DNA replication and division (G1 → S → G2 → M) by which a cell produces two genetically identical daughters, driven by cyclin–CDK complexes and guarded by checkpoints involving p53 and Rb.

Mitosis and Cytokinesis

Overview

Typical duration≈24 h (G1 11 h, S 8 h, G2 4 h, M 1 h)
DNA content2C in G1 → 4C after S phase
TP53 locus17p13.1; mutated in ≈50 % of cancers

Interphase occupies most of the cycle. In G1 (gap 1) the cell grows, makes proteins and organelles and "decides" whether to divide; in S phase it replicates its DNA (2n, 2C → 2n, 4C) and duplicates its centrosome; in G2 it continues growth and checks that replication is complete. M phase comprises mitosis (nuclear division) and cytokinesis. Cells that stop dividing exit into G0, a quiescent state that may be reversible (hepatocytes, fibroblasts, lymphocytes) or permanent (neurons, cardiac myocytes). In a typical human cell cycling every ≈24 h: G1 ≈11 h, S ≈8 h, G2 ≈4 h, M ≈1 h; G1 is the most variable phase.

Progress is driven by cyclin-dependent kinases (CDKs), which are active only when bound to a cyclin; cyclin levels rise and fall through synthesis and ubiquitin-mediated destruction. Cyclin D–CDK4/6 (induced by growth factors) and cyclin E–CDK2 phosphorylate the retinoblastoma protein Rb: hypophosphorylated Rb binds and inhibits the transcription factor E2F; phosphorylation releases E2F, which switches on S-phase genes — passing the restriction point (G1/S), after which the cell is committed to divide even without growth factors. Cyclin A–CDK2 drives S phase; cyclin B–CDK1 (maturation/M-phase promoting factor) triggers mitosis. CDK inhibitors (p21, p27 of the CIP/KIP family; p16 of the INK4 family) brake the cycle.

Checkpoints: the G1/S checkpoint checks DNA damage and cell size — DNA damage activates ATM/ATR, which stabilise p53 (normally kept low by MDM2); p53 induces p21, arresting the cycle for repair, or triggers apoptosis if damage is irreparable. The G2/M checkpoint blocks entry into mitosis with damaged or unreplicated DNA (CHK1 inhibits Cdc25, keeping CDK1 inactive). The spindle-assembly (metaphase–anaphase) checkpoint holds anaphase until all kinetochores are attached to the spindle under tension (Mad2 inhibits APC/C–Cdc20).

Parts & subdivisions

  1. G1 phase
    Growth; restriction point; most variable in length.
  2. S phase
    DNA replication; centrosome duplication.
  3. G2 phase
    Growth and preparation for mitosis; G2/M checkpoint.
  4. M phase
    Mitosis and cytokinesis.
  5. G0
    Quiescence or terminal differentiation.
  6. Cyclin–CDK complexes
    D–CDK4/6 and E–CDK2 (G1/S), A–CDK2 (S), B–CDK1 (M).
  7. Tumour suppressors p53 and Rb
    p53 — "guardian of the genome" (17p13); Rb — gatekeeper of G1/S (13q14).

Function

  • Produces new cells for growth, renewal and repair.
  • Ensures accurate duplication and distribution of the genome.
Physiology

By proliferative capacity, tissues are labile (continuously dividing: epidermis, gut epithelium, bone marrow), stable (normally G0 but can re-enter the cycle after injury: hepatocytes, renal tubular cells, fibroblasts, endothelium) and permanent (cannot divide: neurons, cardiac myocytes; skeletal muscle regenerates only via satellite cells).

Clinical significance

Tumour suppressors and oncogenic viruses

Loss of RB1 causes retinoblastoma (bilateral and early in hereditary cases — Knudson's two hits) and osteosarcoma. Germline TP53 mutation causes Li–Fraumeni syndrome (sarcomas, breast cancer, brain tumours, adrenocortical carcinoma, leukaemia). High-risk HPV proteins E6 (degrades p53) and E7 (inactivates Rb) drive cervical and oropharyngeal cancer.

Cell-cycle drugs

CDK4/6 inhibitors (palbociclib, ribociclib) treat hormone-receptor-positive breast cancer. Cell-cycle-specific chemotherapy: S phase — methotrexate, 5-FU, hydroxyurea, cytarabine; G2 — bleomycin, etoposide; M phase — vinca alkaloids, taxanes.

Mnemonics

Cell cycle order

"Go Sally Go! Make Children" — G1, S, G2, Mitosis, Cytokinesis.

Test yourself

After ionising radiation, p53 halts the cell cycle in G1 mainly by inducing:
  1. Cyclin D
  2. The CDK inhibitor p21
  3. MDM2 degradation of Rb
  4. Telomerase

Answer: The CDK inhibitor p21

DNA damage activates ATM/ATR kinases, which stabilise p53. p53 transcribes p21 (CIP1/WAF1), which inhibits G1/S cyclin–CDKs, keeping Rb hypophosphorylated and E2F sequestered. If damage is irreparable p53 triggers apoptosis (BAX, PUMA, NOXA).

More cells & tissues questions

Compiled from standard anatomy and physiology references — see the Cells & Tissues sources. For education only; not medical advice.