Biology › Cell cycles, reproduction and development › The cell cycle: growth, copying, and one division that changes nothing

The cell cycle: growth, copying, and one division that changes nothing

Mitosis gets the attention and the mnemonic, but in a cell cycling in about a day it occupies roughly a tenth of the time. The other nine tenths are where the DNA is copied and the copy is checked, and that is where the answers to most exam questions on this topic actually live.

Before this DNA structure and replication · Eukaryotic cell ultrastructure

What you should be able to do

• Describe what happens in each phase of the cell cycle, and say which phase takes longest.
• State what each of the three checkpoints checks, and what becomes of a cell that fails one.
• Explain why a chromosome has two chromatids before mitosis and one after it.
• Put the four stages of mitosis in order and say what defines each one, including what the spindle does.
• Calculate a mitotic index from a count of cells and interpret what it means.
• Describe binary fission in a prokaryote and set it against mitosis in a eukaryote.
• Explain how uncontrolled cell division leads to a tumour, using the cycle's checkpoints.

Three phases before anything divides

A cell that is going to divide works through the same sequence every time. In G1 it grows and makes more of the organelles it will have to share out. In S phase it replicates its DNA, semi-conservatively, so that every chromosome ends up as two identical sister chromatids held together at a centromere. In G2 it keeps growing and checks the copy for errors. Only then does mitosis begin.

That ring is drawn for a cell cycling in about 24 hours, and the proportions are a typical case rather than a constant of nature. G1 stretches and shrinks: a root-tip meristem cell runs the whole cycle in a few hours, and mitosis then takes a larger share of a smaller total. Keep the ordering, which never changes, and treat the exact tenth as a figure attached to a 24-hour cycle.

Some cells leave the cycle. A neurone or a mature muscle fibre stops at the end of G1 and enters G0, which is less a phase than the exit from one: it never replicates its DNA again. Most of your cells are in G0 now.

The chromosome count does not change during S phase, which trips people up. A human cell in G1 has 46 chromosomes; after S phase it still has 46 chromosomes, but each one is now two chromatids, so there is twice as much DNA. Count centromeres, not strands, and the arithmetic behaves.

Chromatid

One of the two identical copies of a chromosome, joined to its sister at the centromere after DNA replication.

Homologous pair

Two chromosomes of the same size carrying the same genes at the same loci, one inherited from each parent — not the same thing as a pair of chromatids.

Spindle

The framework of protein microtubules built across the cell before the chromosomes are moved, running from pole to pole and attaching to every centromere; shortening the fibres is what separates the chromatids.

Mitotic index

The proportion of cells in a sample that are visibly in mitosis.

What each checkpoint actually asks

Between the phases sit checkpoints, worth knowing by what they check rather than by name. Each is a point the cycle will not pass until one question is answered yes, and the asking is done by the cell's own proteins — which is why a mutation in one of them matters so much.

The G1 checkpoint is the point of no return. A cell that passes it is committed to copying its entire genome whether conditions stay favourable or not, so cell size, nutrients, signals from neighbours and DNA damage all get their say here. A cell that fails drops back into G0.

The G2 checkpoint is a proofreading stop. S phase copies about three thousand million base pairs in a human cell and does not do it flawlessly, so this checkpoint refuses a cell with unrepaired breaks. Damage that gets past is handed to both daughters.

The spindle checkpoint sits inside mitosis rather than between two phases, and it is why anaphase is so abrupt: one chromosome not yet attached to both poles holds the whole cell at metaphase, and when the last attachment is made every centromere divides at once.

Keep two words apart. A checkpoint delays the cycle, and most cells held at one repair the fault and go on. Apoptosis ends the cell, and is the fallback when repair fails — the tissue between your fingers in the womb was removed by it.

Four stages, and what defines each one

Mitosis is conventionally split into four stages. The split is a convenience — the process runs continuously — but the stages are defined by things you can actually see down a microscope, which is why they are examinable and why you can be handed a photograph and asked to identify one.

The spindle earns its own paragraph, because two of the four stages are defined by what it is doing. It is a framework of protein microtubules, assembled during prophase and running from one pole of the cell to the other. In an animal cell the poles are organised by a pair of centrioles; a plant cell builds the same spindle without them, which is a favourite one-mark question. Fibres attach to every centromere from both sides, and anaphase is those fibres shortening.

Cytokinesis follows, and it is not part of mitosis proper: mitosis divides the nucleus, cytokinesis divides the cytoplasm. In animal cells a ring of protein filaments under the membrane contracts and pinches it inwards. In plant cells it cannot, because of the cell wall, so vesicles line up along the middle, fuse into a cell plate, and a new wall is built outwards from it. Organelles are shared out roughly rather than counted, which is one of the few imprecise things about mitosis.

Counting cells: the mitotic index

The mitotic index is the one calculation this topic asks for, and it comes out of a practical you can run with an onion and a bottle of stain. The tip of a root is a meristem: a few millimetres in which every cell is still dividing. Cut more than 5 mm back and you are into cells that have left the cycle and begun elongating.

The preparation decides whether the count is worth anything. The tip is warmed in dilute hydrochloric acid, which breaks down the middle lamella holding the cells together, then stained — toluidine blue or acetic orcein, both chosen because they bind to DNA — and squashed under a coverslip to a single layer. Two overlapping layers cannot be scored, because a chromosome in one plane of focus looks much like a chromosome in another.

Then the counting, which is where the marks are. Score every cell in the field rather than the interesting ones, because a sample chosen by eye is a sample chosen for cells in mitosis. Count several fields and add them, and state the total: an index without its denominator is an opinion.

One inference the index licenses, and one it does not. A fixed slide is a snapshot of a population, so the fraction caught in a stage is the fraction of the cycle that stage occupies: cycle 20 hours, index 0.15, mitosis about 3 hours. What it cannot tell you alone is how fast the tissue divides, since equal indices mean different rates when the cycles differ in length.

Division that is not mitosis

Mitosis is a eukaryote's answer to a eukaryote's problem: a nuclear envelope to take down and rebuild, and several long linear chromosomes to sort without tangling. A prokaryote has neither, and divides by binary fission. The circular DNA molecule is replicated and the two copies attach to the cell surface membrane at separate points; plasmids are replicated too, though not to a fixed number. The cell grows, carrying the attachment points apart, and a new membrane and wall are laid down across the middle.

Three differences from mitosis are worth having ready. No spindle. No nuclear envelope to break down or re-form. And no chromosomes in the sense used above, so an answer saying 'the chromosomes line up' has imported the wrong process. Binary fission is also fast: Escherichia coli divides in twenty minutes in good conditions, against the day a human cell takes.

The other division a specification asks about is meiosis, a different tool for a different job, with a lesson of its own later in the course. The boundary is what to carry from here: everything above is the division that changes nothing.

When the controls fail

Every daughter cell from mitosis is genetically identical to the parent, which is what makes mitosis the right tool for growth, for repair, and for asexual reproduction. It is also what makes a fault in the process serious: an error is copied faithfully into everything descended from that cell.

Mutations in the genes controlling the checkpoints can leave a cell dividing when it should have stopped. Two categories matter. Proto-oncogenes normally stimulate division, and a mutation can leave one permanently switched on. Tumour suppressor genes normally halt the cycle at a checkpoint, and a mutation can switch one off. Either way the cycle loses a brake, division continues unchecked, and a mass of cells accumulates: a tumour.

That also explains why many chemotherapy drugs work the way they do. Some prevent DNA replication in S phase, some disrupt spindle formation so metaphase cannot complete. Neither targets cancer cells specifically — they target dividing cells — which is why hair follicles and the gut lining, both dividing rapidly, suffer the familiar side effects.

In the exam

• Say which phase, not just 'interphase'. G1, S and G2 do different things and questions distinguish them.
• After replication a cell has the same number of chromosomes and twice the DNA. Questions using DNA mass against time are testing exactly that.
• Anaphase begins when the centromeres divide. If you are identifying a stage from a photograph, that is the observable event to look for.
• Cytokinesis is not a stage of mitosis, and plant and animal cells do it differently. Both facts are single marks that get thrown away.
• Mitotic index is a proportion of the cells you counted, so state the total you counted from. An index without a denominator is not a measurement.
• Name the spindle. 'The chromosomes cannot separate' is half an answer; 'the fibres cannot attach to the centromeres, so metaphase never completes' is the whole one.

Questions

Written to the command words the boards use. Try them on paper before opening a scheme: the marks go to points made, not to length.

← Translation: turning a message into a working protein · Why nothing large can breathe through its skin →