AS 5 The mitotic cell cycle | A Level Biology 9700

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🎯What you need to be able to do

Describe chromosome structure: DNA, histone proteins, sister chromatids, centromere and telomeres.
Explain the importance of mitosis in growth, replacement, repair and asexual reproduction.
Outline the mitotic cell cycle: interphase (G₁, S, G₂), mitosis and cytokinesis.
Outline the role of telomeres in preventing the loss of genes during DNA replication.
Outline the role of stem cells in cell replacement and tissue repair.
Explain how uncontrolled cell division results in a tumour.
Describe chromosome behaviour through prophase, metaphase, anaphase and telophase, and identify these stages in micrographs and slides.

📚The biology

What a chromosome is made of

A chromosome is one very long DNA molecule wound around histone proteins, which package it so that a length measured in centimetres fits inside a nucleus a few micrometres across, and which help control access to the genes.

After DNA replication in the S phase, each chromosome consists of two identical sister chromatids joined at the centromere. The chromatids are copies of each other; they are not a homologous pair, which is a different idea belonging to meiosis. At each end of the DNA molecule is a telomere, a repetitive non-coding sequence.

A chromosome is not always two chromatids. Before S phase it is a single DNA molecule; after S phase and until anaphase it is two chromatids; from anaphase onwards each separated chromatid is itself called a chromosome. Questions that ask “how many chromosomes are present at metaphase?” are testing exactly this, and the answer is the diploid number, not twice it.

Why telomeres matter

DNA polymerase cannot replicate right to the very end of a strand, so a short length is lost from each end at every round of replication. Telomeres are non-coding repeat sequences that sit at the ends as a sacrificial buffer: it is telomere that is shortened, not genes. Without them, useful genes would be trimmed away within a few divisions.

The cell cycle

Interphase — much the longest stage, and the reason most cells on a slide are in it.
- G₁ — growth; organelles and proteins are synthesised.
- S — DNA replication; each chromosome becomes two sister chromatids.
- G₂ — further growth; the cell prepares for division.
Mitosis — nuclear division, producing two genetically identical nuclei.
Cytokinesis — division of the cytoplasm into two cells. In animal cells the membrane pinches inwards; in plant cells a cell plate forms across the middle and a new wall is laid down, because the existing wall cannot constrict.

The importance of mitosis

Mitosis produces genetically identical daughter cells, which matters for:

growth of a multicellular organism from a zygote;
replacement of damaged or dead cells, such as red blood cells and skin;
repair of tissues by cell replacement;
asexual reproduction, which produces offspring identical to the parent.

Stem cells

A stem cell is an unspecialised cell that can divide repeatedly by mitosis and whose daughter cells can differentiate into specialised types. Stem cells in bone marrow replace blood cells; stem cells at the base of the epidermis replace skin; in plants, meristem cells do the equivalent job. They are the reason a tissue with a short-lived cell population can be maintained for a lifetime.

Tumours

Cell division is normally controlled by genes that regulate the cycle. A mutation in those genes can leave a cell dividing continuously and uncontrollably, ignoring the signals that would normally stop it. The resulting mass of cells is a tumour. A benign tumour stays in one place; a malignant one invades surrounding tissue and cells may break away and spread (metastasis), which is cancer. Mutations accumulate over time and are made more likely by mutagens such as ionising radiation, tobacco tar and some viruses.

Chromosome behaviour in mitosis

Learn each stage by what you can see, because that is what the slide shows.

Prophase — chromosomes condense and become visible as two chromatids joined at a centromere. The nuclear envelope breaks down and the nucleolus disappears. Centrioles (in animal cells) move to opposite poles and the spindle forms from microtubules.
Metaphase — chromosomes line up on the equator, attached by their centromeres to spindle fibres from both poles.
Anaphase — centromeres divide and the sister chromatids are pulled apart to opposite poles as the spindle fibres shorten. On a slide this is the V-shaped stage, with the centromere leading. It is the shortest stage, so the rarest to find.
Telophase — chromatids reach the poles and decondense; a nuclear envelope re-forms around each group and nucleoli reappear. The spindle breaks down. Cytokinesis usually begins.

The cell surface membrane is involved at cytokinesis; the spindle is what physically moves the chromosomes, and it needs ATP.

✏️Worked example

A student examined a stained squash of onion root tip and counted the cells in each stage of the cell cycle across five fields of view: interphase 372, prophase 58, metaphase 22, anaphase 9, telophase 39. (a) Calculate the mitotic index, to three significant figures. (b) The complete cell cycle in this tissue takes 20 hours. Estimate the length of anaphase. (c) Explain why the root tip was chosen, and why anaphase cells are hardest to find.

(a) The mitotic index is the proportion of cells visibly in mitosis. Cells in mitosis = 58 + 22 + 9 + 39 = 128. Total cells = 372 + 128 = 500.

\[ \text{mitotic index} = \frac{128}{500} = 0.256 \]

or 25.6% if the question asks for a percentage. Give the units or the % sign as asked, and do not round to 0.26 when three significant figures were specified.

(b) The proportion of cells caught in a stage is proportional to the time the stage occupies, because the sample is a snapshot of a population dividing asynchronously. Anaphase is 9 out of 500 cells, so

\[ \frac{9}{500} \times 20\ \text{hours} = 0.36\ \text{hours} = 21.6\ \text{minutes} \]

(c) The root tip contains the meristem, where cells are actively dividing by mitosis, so a high proportion of cells are in some stage of division and the count is worth doing. Tissue taken further up the root has stopped dividing and would show almost nothing but interphase.

Anaphase cells are rare because anaphase is the shortest stage — here about 22 minutes out of a 20-hour cycle, roughly 2% of the time. At any instant only about 2% of cells are in it, so it is the stage you must hunt for.

Check it. Two checks. The five counts must sum to the total you divide by — 500 here — and interphase must be much the largest group, which it is at 372 of 500 (74%). If your count showed more cells in mitosis than in interphase, you have either miscounted or misidentified condensed nuclei. Second, the stage times must sum to the cycle length: 0.256 × 20 = 5.1 hours in mitosis and 14.9 hours in interphase, which is the expected shape for a meristem.

Leaving interphase out of the denominator. The mitotic index is cells in mitosis divided by the total number of cells, not by the number of dividing cells. Using 128/128 or 9/128 is the standard error and gives a nonsensical answer. Second trap: cytokinesis is not a stage of mitosis, so a cell showing a cell plate is usually counted as telophase — and interphase cells are not “resting”, they are the busiest of all, replicating DNA and growing.

📝Practise

Work through these, then reveal the answer. Each question targets a different objective from the list above.

1. Describe what happens to the chromosomes and the nuclear envelope in prophase and in telophase.

Prophase: the chromosomes condense (coil and shorten) and become visible under a light microscope, each already consisting of two sister chromatids joined at a centromere because DNA replicated in the preceding S phase. The nuclear envelope breaks down and the nucleolus disappears; the spindle begins to form. Telophase: the separated chromatids, now at the poles, decondense (uncoil and lengthen) and become indistinct; a nuclear envelope re-forms around each group, so two nuclei are present; nucleoli reappear and the spindle breaks down. Telophase is essentially prophase in reverse, which is a useful way to remember it.

2. Explain why mitosis produces genetically identical daughter cells, referring to two specific events.

First, semi-conservative DNA replication in the S phase produces two identical copies of each DNA molecule, held together as sister chromatids — the base-pairing rules ensure the copies match the original exactly. Second, at anaphase the centromeres divide and one chromatid from each pair is pulled to each pole, so each daughter nucleus receives exactly one copy of every chromosome. There is no crossing over and no independent assortment of homologous pairs, unlike meiosis. The two events together mean each daughter cell has the same number of chromosomes and the same alleles as the parent cell — identical apart from any rare replication error.

3. A student states that telomeres ‘protect the chromosome from damage’. Give the more precise syllabus explanation.

Telomeres are repetitive, non-coding DNA sequences at the ends of each chromosome. DNA polymerase cannot replicate the extreme end of a DNA strand, so a short length is lost at every round of replication. Because the sequence lost is telomere rather than coding DNA, telomeres prevent the loss of genes from the ends of chromosomes. They act as a sacrificial buffer, shortening progressively with successive divisions. The student’s answer is not wrong so much as unearned — the mark is for identifying the replication problem and the non-coding buffer, not for the general idea of protection.

4. Distinguish between a benign and a malignant tumour, and explain how both arise from the same underlying failure.

Both arise when mutations in the genes controlling the cell cycle leave cells dividing continuously and uncontrollably, ignoring the normal signals that stop division, so a mass of cells accumulates. A benign tumour remains localised in one place, often enclosed, and grows slowly; it causes harm only by pressing on surrounding tissue. A malignant tumour invades surrounding tissue, and cells can break away, travel in the blood or lymph and form secondary tumours elsewhere (metastasis); this is cancer. The distinction is behavioural, not a difference in the original cause: it is the same loss of cell cycle control, with additional mutations conferring the ability to invade.

5. A tissue has a cell cycle lasting 24 hours, of which mitosis occupies 90 minutes. Predict the mitotic index and explain your reasoning.

In an asynchronously dividing population, the proportion of cells found in a stage is proportional to the fraction of the cycle that stage occupies. Mitosis is 90 minutes out of 24 × 60 = 1440 minutes, so the expected mitotic index is 90/1440 = 0.0625, or 6.25%. In a sample of 400 cells you would therefore expect roughly 25 in some stage of mitosis and 375 in interphase. The reasoning assumes that cells are not synchronised and that the sample is representative — a real count would vary between fields of view, which is why several fields and a large total count are used.

6. A micrograph shows a plant cell with chromatids at opposite poles and a structure forming across the middle of the cell. Identify the stage or stages and justify.

Chromatids that have arrived at the poles place the cell in telophase — in anaphase they would still be moving, appearing V-shaped with the centromere leading. The structure across the middle is the cell plate, which is cytokinesis beginning. So the cell is in telophase with cytokinesis under way; the two overlap. Note that cytokinesis is not a stage of mitosis — mitosis is nuclear division only — and that the cell plate identifies this as a plant cell: an animal cell divides by the membrane constricting inwards to form a cleavage furrow, because it has no wall to build.

🔗Go deeper — other people’s work

These are external resources, not mine. If one stops working, tell me and everything above it on this page still stands.

The Cell Image Library and CellsAlive — annotated micrographs of every mitotic stage in onion root tip, which is the tissue Paper 3 uses
Any onion root tip squash practical video — the acid hydrolysis and staining steps are worth seeing once before you attempt them
Cancer Research UK — a clear public-facing account of how cell cycle mutations lead to tumours, useful for the ‘discuss’ style questions