Cell division and mitosis

Your body is making new cells all the time. That is how you grow, and how a cut on your finger heals over.

A cell makes a new cell by copying everything inside itself and then splitting into two. The trickiest part is sharing out the DNA, the instruction manual for the whole cell, so that each of the two new cells ends up with a complete set.

The DNA is packed into little bundles called chromosomes. First the cell copies each chromosome, so it has two of each. Then it lines the copies up in a row down the middle. Spindle fibres reach in from both ends and pull one of each pair to opposite sides. Finally the cell pinches in the middle and separates into two. The two new cells are identical to the one you started with. This whole orderly process is called mitosis.

Most of a cell's life is spent not dividing, in a long stretch called interphase. It has three parts. In G1 the cell grows and goes about its normal job. In S phase it copies its DNA, so every chromosome becomes two identical strands. In G2 it does a final check and a bit more growth. Only then does it enter mitosis (M), the short and dramatic part where the copied chromosomes are separated, followed by cytokinesis, when the cell itself divides in two.

Mitosis runs through named stages that flow into one another. In prophase the long, loose DNA winds up tight into compact chromosomes you could see under a microscope. Because the DNA was copied back in S phase, each chromosome is now two identical sister chromatids, joined at a pinched waist called the centromere. Around the same time a scaffold of protein fibres, the spindle, begins to build out from opposite ends of the cell.

In metaphase the chromosomes are shuffled into a single line across the middle of the cell, on an imaginary plane called the metaphase plate. Each one is held in place by spindle fibres reaching in from both poles.

Anaphase is the split. The link holding each pair of sister chromatids lets go, and the spindle fibres draw one chromatid from every chromosome toward each pole. Now both ends of the cell hold a full, matching set.

In telophase a fresh nuclear envelope gathers around each of the two sets, so for a moment the cell has two nuclei, and the chromosomes relax back into working DNA. Cytokinesis then squeezes the cell down the middle. In animal cells a ring of protein tightens like a drawstring until the cell splits into two separate daughter cells.

The cell does not just barrel through all this. At certain checkpoints it pauses to make sure the DNA is undamaged and fully copied, and that every chromosome is properly hooked up to the spindle, before it allows the next step to begin. Get those wrong and a daughter cell could end up with the wrong number of chromosomes.

Mitosis makes two identical copies for growth and repair. A different kind of division, meiosis, makes egg and sperm cells instead: it halves the chromosome number and reshuffles the genes, which is part of why children are not exact clones of either parent.

The engine: cyclins and CDKs

The cycle is driven forward by enzymes called cyclin-dependent kinases (CDKs). A CDK is only active when it is bound to a partner protein, a cyclin, and the various cyclins rise and fall in a set order through the cycle. Each surge switches on the CDK activity that pushes the cell from one phase into the next, so the sequence advances in one direction and does not slip back.

Holding anaphase: the spindle assembly checkpoint

Before the sisters are allowed to part, every chromosome must be attached correctly, its two kinetochores gripped by microtubules that reach in from opposite poles. That bi-orientation is what the cell is really checking for. Any kinetochore still unattached keeps broadcasting a wait signal, the spindle assembly checkpoint, which blocks the onset of anaphase. Only when the last chromosome is properly attached does the signal lift.

Cutting the tie: cohesin and separase

Sister chromatids are held together along their length by a protein ring called cohesin. At the metaphase-to-anaphase transition the checkpoint releases and an enzyme called separase cleaves that cohesin. With the glue gone, the tension already loaded into the spindle snaps the sisters apart toward the poles.

When it goes wrong: aneuploidy and cancer

If chromosomes separate unevenly, a daughter cell inherits too many or too few, a state called aneuploidy, which lies behind many miscarriages and conditions such as Down syndrome. More broadly, cancer is a disease of lost cell-cycle control: mutations that disable tumour suppressors such as p53 or Rb, or that jam oncogenes in the on position, let cells keep dividing when they should have stopped.

A built-in counter

Normal human cells cannot divide forever. Each division shortens the protective caps on the chromosome ends, the telomeres, and once they wear too short the cell stops dividing, a ceiling known as the Hayflick limit.