Mitosis — How Cells Divide

Your body started as a single cell — one fertilised egg. Today you have around 37 trillion cells. Every single one of those cells came from that original cell dividing, and dividing, and dividing again. Cell division is not just about growth. Your body replaces cells constantly: - The lining of your gut is completely replaced every 3–5 days - Red blood cells live for about 120 days, then are replaced - Skin cells are shed and replaced roughly every 2–4 weeks - Some cells (like neurons and heart muscle cells) divide very rarely or not at all There are two types of cell division in the human body: - Mitosis — makes identical copies for growth and repair (this lesson) - Meiosis — makes sex cells (eggs and sperm) with half the usual chromosomes (next lesson) What mitosis produces: One cell goes in → two identical daughter cells come out. Each daughter cell is genetically identical to the parent cell and has the full set of 46 chromosomes. Mitosis is used for everything except making eggs and sperm.

A cell does not just divide constantly. It spends most of its life doing its regular job — then prepares carefully before dividing. This preparation + division cycle is called the cell cycle. The cell cycle has two main phases: Interphase — the preparation phase (takes up ~90% of the cycle): This is NOT a resting phase — the cell is extremely busy. - G1 phase (Gap 1) — the cell grows larger, makes proteins, and checks that everything is ready to proceed. Cells can pause here for hours, days, or permanently (neurons rarely divide again once mature — they stay in G1 permanently, a state called G0). - S phase (Synthesis) — the cell copies ALL of its DNA. Every one of the 46 chromosomes is duplicated, so the cell temporarily has 92 chromosomes (in duplicate pairs). This takes about 6–8 hours. - G2 phase (Gap 2) — the cell double-checks the DNA copies for errors, continues growing, and assembles the machinery needed for division. M phase — actual division: This is mitosis + cytokinesis (splitting the cytoplasm). The cell splits into two. Cell cycle checkpoints — quality control: There are three major checkpoints where the cell checks everything is correct before proceeding: - G1 checkpoint — is the cell big enough? Is DNA undamaged? Are conditions right? - G2 checkpoint — has DNA been copied correctly? Are there any errors? - Spindle checkpoint — are all chromosomes correctly attached to the spindle fibres? If anything is wrong, the checkpoint can pause the cycle for repair — or trigger apoptosis (programmed cell death) if the damage is too severe. The protein p53 is the key checkpoint enforcer. Loss of p53 is found in ~50% of all human cancers — without this gatekeeper, damaged cells keep dividing instead of stopping.

Mitosis itself — the actual division of the nucleus — is divided into four stages. A helpful memory trick: PMAT (Prophase, Metaphase, Anaphase, Telophase). Prophase — "Preparing": The duplicated chromosomes condense (wind up tight so they can be moved without tangling). Each chromosome now consists of two identical strands joined at a point called the centromere — these joined strands are called sister chromatids. The nuclear envelope (membrane around the nucleus) breaks down. The spindle apparatus — a framework of protein fibres called microtubules — begins to form at two poles of the cell. Metaphase — "Middle": The chromosomes line up in a single line along the centre of the cell (the metaphase plate). Spindle fibres from each pole attach to each chromosome's centromere. This is the stage where chromosomes are most visible under a microscope — this is when karyotypes (chromosome photographs) are taken to check for chromosomal abnormalities. Anaphase — "Apart": The spindle fibres contract and pull the sister chromatids apart toward opposite poles. Each pole now receives one copy of every chromosome. This separation is the critical moment — if it goes wrong (non-disjunction), one cell gets an extra chromosome and another gets too few. Telophase — "Two nuclei": A new nuclear envelope forms around each set of chromosomes. The chromosomes decondense (unwind) back to their loose working state. The spindle fibres disassemble. Cytokinesis — splitting the cell: Technically after mitosis, cytokinesis is the physical splitting of the cytoplasm. In animal cells, a ring of protein fibres (actin) contracts like a drawstring around the middle of the cell, pinching it into two separate cells. Each daughter cell gets roughly equal amounts of cytoplasm and organelles. Total time for mitosis + cytokinesis: about 1–2 hours in rapidly dividing human cells.

Mitosis is normally a tightly controlled process. When that control breaks down, cells can divide uncontrollably — producing a tumour. What is cancer? Cancer is essentially a disease of uncontrolled cell division. Normal cells receive signals telling them when to divide and when to stop. Cancer cells ignore these signals — they divide when they should not, refuse to die when they should, and can invade neighbouring tissues. How does mitosis go wrong? Two types of gene normally control cell division: - Proto-oncogenes — genes that normally promote cell division when needed (like the accelerator in a car). A mutation can convert them into oncogenes — the accelerator gets stuck on. - Tumour suppressor genes — genes that normally slow or stop cell division (the brakes). Mutations can knock these out — the brakes fail. Cancer usually requires multiple mutations in both types of gene — which is why it typically develops over years or decades, and why it becomes more common with age (more time for mutations to accumulate). Non-disjunction and chromosomal abnormalities: If chromosomes fail to separate properly during anaphase (non-disjunction), daughter cells end up with the wrong number of chromosomes. In cancer cells, the chromosome number is often wildly abnormal. In early development, non-disjunction during meiosis can cause Down syndrome (an extra chromosome 21 — trisomy 21), Turner syndrome (missing an X chromosome — 45,X), and other conditions. Why this matters for medicine: Understanding the cell cycle has led directly to cancer treatments. Many chemotherapy drugs work by targeting rapidly dividing cells — for example, by blocking DNA replication (S phase) or preventing spindle formation (M phase). Radiation therapy damages DNA to trigger the cell's own checkpoint-driven apoptosis. Targeted therapies (like imatinib for leukaemia) block specific mutated proteins that drive uncontrolled division.

Not all cells divide at the same rate. Understanding which cells divide — and how — is central to understanding both health and disease. Rapidly dividing cells (high mitotic rate): - Gut lining (enterocytes) - Blood cells (from bone marrow stem cells) - Skin cells (keratinocytes) - Hair follicle cells These cells are most vulnerable to chemotherapy (which targets dividing cells) — which is why cancer patients often lose hair and suffer gut problems and low blood counts during treatment. Slowly or rarely dividing cells: - Liver cells — can divide when needed but usually do not - Kidney cells — limited regeneration - Skeletal muscle cells — repair by fusion, not simple division Effectively non-dividing cells: - Neurons (most types) — once lost, generally cannot be replaced - Cardiac muscle cells — very limited regeneration This is why heart attacks (killing cardiac muscle) and strokes (killing neurons) cause permanent damage — these cells cannot replace themselves through mitosis. Apoptosis — planned cell death: Just as important as cell division is controlled cell death. Apoptosis (from Greek: "falling off", like leaves from a tree) is the cell's built-in self-destruct programme. It is tidy — the cell packages up its contents and is cleanly cleared away without causing inflammation. Apoptosis is essential for: - Sculpting body parts during development (the spaces between your fingers form by apoptosis of the cells between them) - Eliminating damaged or potentially cancerous cells - Removing immune cells after an infection is cleared When apoptosis fails — when cells that should die instead survive — this is another key step in the development of cancer.