Mitosis: How One Cell Makes Two Identical Cells

1One nucleus becomes two

Right now, somewhere in a living body, cells are finishing a copy of their DNA and then splitting it perfectly in two. The result is two cells that are genetically identical to the parent. The process that shares the copied chromosomes is mitosis.

The BC curriculum defines it simply: mitosis is the process through which pre-existing cells make two identical copies of themselves. That definition hides a lot of choreography. Chromosomes must condense, line up, split and travel, all without a single one being lost. This lesson follows that choreography step by step.

Mitosis is easier to follow with a model cell. The diagrams here use a cell with only four chromosomes: two coloured one way and two another, to show that chromosomes come in homologous pairs (one set from each parent). A human cell has 46, but the steps are the same.

2The stages of mitosis, in order

Mitosis is a continuous process, but scientists divide it into named stages so that it is easier to talk about. The stages blend into one another; a real cell does not stop at the boundaries.

Before mitosis: interphase and DNA copying

By the time mitosis begins, the S phase has already copied every chromosome. Each chromosome consists of two sister chromatids joined at the centromere. The centrosome (the organizer of the spindle) has also been duplicated. If mitosis began without this preparation, the daughter cells would receive only half of the instructions.

The five phases

1. Prophase. The loosely spread chromatin winds up tightly into visible chromosomes. The nucleolus disappears, and the nuclear envelope breaks into small vesicles. The two centrosomes move to opposite ends (poles) of the cell, and the spindle, a framework of tiny tubes called microtubules, grows between them.
2. Prometaphase. The remnants of the nuclear envelope fragment further. Each sister chromatid develops a protein structure called a kinetochore at its centromere. Spindle fibres from opposite poles attach to the kinetochores, so that each of the two sister chromatids faces a different pole. (Many introductory courses fold this stage into prophase or metaphase.)
3. Metaphase. The spindle fibres tug the chromosomes until they line up along the cell's middle, an imaginary plane called the metaphase plate. Chromosomes are at their most condensed here, which is why metaphase is the stage most often used for pictures of chromosomes. A checkpoint confirms that every chromosome is properly attached before the cell continues.
4. Anaphase. The proteins holding sister chromatids together are broken down, and the sister chromatids separate at the centromere. Each chromatid is now counted as a full chromosome and is pulled towards the pole its fibre leads to. The cell also elongates as the poles move apart.
5. Telophase. The chromosomes reach the poles and unwind back into loose chromatin. The spindle breaks down, and a nuclear envelope re-forms around each set of chromosomes. The cell now has two nuclei.

3Cytokinesis: dividing the rest of the cell

Mitosis moves the chromosomes, but a cell is more than a nucleus. The cytoplasm, organelles and membrane must also be divided. This is cytokinesis. It usually starts in late anaphase and finishes after telophase.

In animal cells

A ring of protein fibres (actin) forms just inside the cell membrane around the middle of the cell, where the metaphase plate was. As the ring tightens, it pulls the membrane inward, creating a groove called the cleavage furrow. The furrow deepens until the cell pinches into two. A useful comparison is the drawstring of a bag pulled tight.

In plant cells

Plant cells are surrounded by a stiff wall, so they cannot simply pinch. Instead, small membrane-bound packages called vesicles, carrying building materials, gather in the centre of the cell and fuse into a flat structure called the cell plate. The plate grows outward until it reaches the existing walls. The materials are then used to build a new wall between the two daughter cells, and the vesicle membranes become the new cell membranes.

Cytokinesis does not always happen. If it is skipped after mitosis, the result is a single cell with more than one nucleus. Both outcomes show that mitosis (nuclear division) and cytokinesis (cell division) are two separate steps.

4Why the daughter cells are identical

The result of mitosis is two cells with the same number and type of chromosomes as the parent cell. Two features of the process guarantee this.

• The DNA is copied exactly once. The sister chromatids in each chromosome are identical copies.
• The sister chromatids are pulled to opposite poles. Each new cell receives exactly one copy of every chromosome. The spindle checkpoint helps to make sure that no chromosome is attached to only one pole.

“Identical” refers to the DNA that is passed on. Small copying errors (mutations) can happen, but they are rare, and cells have repair and checkpoint systems to catch many of them. The daughter cells can also differ in other ways, for example in how the cytoplasm is divided.

5Mitosis at work in a body

Mitosis is the main type of cell division used by eukaryotic organisms for growth, repair and replacement. Its jobs in the body include the following.

• Growth. After fertilization, a single cell divides again and again by mitosis. The early divisions produce a ball of smaller and smaller cells, and later divisions build tissues and organs.
• Repair. When skin is scraped, cells near the wound divide to replace those that were lost.
• Replacement. Many cells wear out and are replaced by new ones made through mitosis.
• Asexual reproduction. In some single-celled eukaryotes and in many multicellular organisms, mitosis creates new individuals without a partner. This is the topic of the next lesson.

6When the controls fail: cancer

Because mitosis produces more cells, it must be tightly controlled. Cells normally divide only when needed, and checkpoints pause the cycle when something is wrong. Cancer is a group of diseases caused by uncontrolled cell growth.

The story usually begins with DNA copying errors. Even with checkpoints in place, a small share of errors in S phase may get through and be passed on to daughter cells. Errors can also be caused by damage to DNA. If the errors build up in genes that control the cycle, the controls weaken. Two kinds of genes matter most.

• Genes for “accelerators”. Normal genes called proto-oncogenes code for proteins that push the cell forward. When altered so that they are overactive, they are called oncogenes and push the cell through the cycle too fast.
• Genes for “brakes”. Tumour suppressor genes code for proteins (such as p53) that stop division when something is wrong. When they are damaged, the brakes fail. A damaged form of p53 is found in more than half of human tumour cells.

Cells that no longer respond to the controls can outgrow their neighbours and form a lump called a tumour. In short: the cell cycle and its checkpoints are what stand between a healthy body and runaway growth.

Reading mitosis under a microscope

Identifying stages in a photograph or slide of dividing cells is a standard skill. A few clues make it manageable.

1. Is a nuclear envelope visible? If a clear round nucleus is visible and no distinct chromosomes can be seen, the cell is in interphase.
2. Are chromosomes visible as separate threads or rods? If so, and no line-up is visible, the cell is in prophase (or prometaphase).
3. Are chromosomes in a line across the middle? Metaphase.
4. Are two groups of chromosomes moving apart? Anaphase, often with V-shapes pointing toward the poles.
5. Are there two separate groups at opposite ends, with new nuclear envelopes or a pinching middle? Telophase and cytokinesis.

This links back to the idea from the previous lesson that frozen snapshots of many cells can be used to estimate how long each stage takes.

What if something goes wrong during division?

The spindle checkpoint exists because the stakes are high. Consider what would happen if a single sister-chromatid pair were attached to spindle fibres from only one pole. At anaphase, both chromatids could be dragged to the same side. One daughter cell would then have an extra chromosome and the other would be missing one. Missing or extra chromosomes mean missing or extra copies of many genes, which usually upsets the way a cell works.

This is why the checkpoint holds the cell in metaphase until every chromosome is attached to fibres from opposite poles. The cell treats an unattached chromosome as a reason to wait. Only when everything is in place does it let anaphase start. Thinking this way, the checkpoint is a quality-control step, similar to a pilot running through a checklist before takeoff.

Modelling mitosis

A physical or drawn model is a good way to test whether the stages make sense. A simple model can be built with two colours of string or pipe cleaner, using two pairs of chromosomes as in the diagram.

1. Lay out four single strands: two of one colour (a homologous pair) and two of another colour (a second pair).
2. Show S phase by adding a matching copy next to each strand and twisting each pair together at the middle (the centromere). There are still four chromosomes, but each has two chromatids.
3. Line the four joined pairs along a line down the middle of the table (metaphase).
4. Pull each joined pair apart so one strand goes to each side (anaphase). Count the strands on each side.
5. Draw a circle round each group of strands (telophase and cytokinesis).

The model has limits: real chromosomes are not strings, and real cells do not move chromosomes by hand. Evaluating what a model does and does not show is itself part of scientific thinking. Even so, each side ends up with four strands that match the original set, which captures the main outcome of mitosis.

7Summary

• Mitosis follows interphase and divides the nucleus into two identical nuclei: prophase, (prometaphase), metaphase, anaphase, telophase.
• Cytokinesis divides the cytoplasm. Animal cells pinch (cleavage furrow); plant cells build a cell plate.
• Because DNA is copied once and sister chromatids are shared equally, the two daughter cells are genetically identical to the parent and to each other.
• Mitosis supports growth, repair and replacement, and, in many organisms, reproduction.
• Failure of cell cycle controls can lead to uncontrolled division and tumours (cancer).

Mitosis makes identical copies. The next lesson shows how organisms use it to reproduce on their own. After that, a different kind of division, meiosis, is needed to produce sex cells.

?Quick check

Try each question first, then reveal the answer.