The eukaryotic cell cycle is an ordered, tightly regulated sequence of events through which a cell grows, replicates its DNA, and divides into two daughter cells. It is divided into two broad phases: Interphase (G1 + S + G2) where the cell prepares for division, and Mitotic phase (M) where actual division occurs. Interphase is the longest phase, often comprising 90% or more of the total cell cycle. The cycle is regulated by cyclin-CDK complexes and checkpoint mechanisms that ensure correct ordering and quality control at each stage.

G1 (Gap 1 or Growth 1) begins immediately after a cell completes division. During this phase: the cell increases in size, synthesises proteins, RNA, and organelles needed for DNA replication, and responds to growth signals. The G1 checkpoint (restriction point) late in G1 is the major decision point of the cell cycle — the cell assesses its size, nutrient availability, DNA integrity, and external growth signals before committing to S phase. If conditions are unfavourable or if the cell has completed its developmental role, it may exit to G0 (quiescent/resting state) instead of proceeding to S phase. Most terminally differentiated cells (neurons, cardiac muscle) remain permanently in G0.

S (Synthesis) phase is when DNA replication occurs. Key events: Each of the 46 chromosomes (in humans) is duplicated by semi-conservative replication — each original strand serves as a template for a new complementary strand, yielding two identical sister chromatids joined at the centromere. DNA content effectively doubles from 2n to 4n equivalent, though chromosome number remains 2n (sister chromatids are counted as ONE chromosome, not two). Histones are also synthesised during S phase to package the newly synthesised DNA into chromatin. Replication begins at multiple origins of replication simultaneously along each chromosome, enabling the enormous human genome (~3.2 billion base pairs) to be replicated within hours. DNA polymerases carry out replication with high fidelity, supported by proofreading mechanisms.

G2 (Gap 2 or Growth 2) phase follows completion of S phase. During G2: cell continues to grow and synthesises proteins specifically needed for mitosis, including tubulin (for spindle fibre formation), condensins (for chromosome condensation), and mitotic kinases. The G2 checkpoint is a critical quality control point: it verifies that DNA replication is complete and checks for DNA damage before allowing progression to M phase. If DNA damage is detected, checkpoint kinases (ATM, ATR, Chk1, Chk2) activate repair pathways and halt the cycle. p53 tumour suppressor is a key regulator at this checkpoint. Failure of G2 checkpoint in cancer cells allows damaged DNA to be passed to daughter cells, contributing to genomic instability.

M phase is the actual division phase, comprising Mitosis (nuclear division) followed by Cytokinesis (cytoplasmic division). Mitosis has four stages: Prophase: chromosomes condense and become visible. Nuclear envelope breaks down. Spindle fibres form from centrioles. Metaphase: chromosomes align at the equatorial plate (metaphase plate). Spindle fibres attach to kinetochores at centromeres. Spindle assembly checkpoint ensures all chromosomes are properly attached. Anaphase: sister chromatids separate and move to opposite poles (pulled by spindle fibres). Cell elongates. Telophase: chromosomes arrive at poles and decondense. Nuclear envelopes reform. Cytokinesis: cytoplasm divides — animal cells use a contractile ring of actin-myosin (cleavage furrow); plant cells form a cell plate from inside outward. Result: two genetically identical daughter cells, each with the same chromosome number as the parent cell.

Three major checkpoints monitor and control cell cycle progression: G1 checkpoint (restriction point): Is the cell large enough? Is DNA intact? Are external growth factors present? This is the primary commitment point — once a cell passes this, it is committed to completing division. G2/M checkpoint: Has all DNA been replicated accurately? Is there any DNA damage? Only if DNA is complete and undamaged does the cell proceed to mitosis. Spindle assembly checkpoint (SAC): During metaphase, ensures ALL chromosomes are properly attached to spindle fibres from both poles before anaphase begins. Just one unattached kinetochore delays the whole process. These checkpoints are enforced by tumour suppressor proteins (p53, Rb) and CDK inhibitors. Cancer commonly involves mutations that bypass these checkpoints, allowing inappropriate proliferation.

Cell cycle progression is driven by cyclin-dependent kinases (CDKs), which are enzymatically active only when bound to specific regulatory proteins called cyclins. Different cyclin-CDK complexes drive different cell cycle transitions: Cyclin D-CDK4/6: active in early G1, phosphorylates Rb protein, releasing E2F transcription factors needed for S phase entry. Cyclin E-CDK2: active at G1/S transition, triggers S phase entry. Cyclin A-CDK2: active during S phase, initiates and maintains DNA replication. Cyclin B-CDK1 (MPF — Maturation Promoting Factor): active at G2/M transition, triggers entry into mitosis by phosphorylating numerous mitotic targets including condensins, nuclear lamins, and spindle assembly factors. Cyclins are periodically synthesised and degraded (via ubiquitin-proteasome pathway), creating oscillating CDK activity that drives irreversible, unidirectional progression through the cycle.

Understanding the cell cycle is fundamental to understanding cancer and its treatment. Cancer cells often show: Mutations in Rb (retinoblastoma) or p53 tumour suppressors, allowing cells to bypass G1 or G2 checkpoints. Overexpression of cyclins (especially Cyclin D and E), driving excessive CDK activity and uncontrolled S phase entry. Loss of spindle assembly checkpoint, allowing aneuploid daughter cells. Many cancer chemotherapy drugs specifically target rapidly dividing cells by interfering with cell cycle phases: S phase drugs: antimetabolites (methotrexate, 5-fluorouracil) inhibit DNA synthesis, hydroxyurea inhibits ribonucleotide reductase. M phase drugs: taxanes (paclitaxel, docetaxel) stabilise microtubules preventing spindle function; vinca alkaloids (vincristine, vinblastine) destabilise microtubules. Targeting the cell cycle remains one of the most effective strategies in cancer therapy.