Chromosomes and the Cell Cycle

AS · 13 min

Every time a eukaryotic cell divides, it must first copy all of its DNA exactly and then share the copies equally between two daughter cells. This note covers the structure that makes this possible, the chromosome, built from DNA and histone proteins with a centromere and telomeres, and the mitotic cell cycle: interphase (G1, S and G2), mitosis and cytokinesis. It also explains how telomeres stop genes being lost from the ends of chromosomes each time DNA is replicated. Questions here often ask you to label a chromosome, describe what happens in each phase, interpret graphs of DNA content and calculate the time spent in each phase.

The structure of a chromosome

In a non-dividing cell, the DNA in the nucleus is spread out as chromatin, a loose complex of DNA and proteins, too thin to see as separate threads with a light microscope. Before a cell divides, the chromatin condenses (coils up much more tightly) into compact chromosomes, which are visible with a light microscope once stained.

Definition

A chromosome is a structure in the nucleus made of one long DNA molecule (or, after DNA replication, two identical DNA molecules) wound around histone proteins. It carries many genes.

The components you need to know are:

  • DNA: each chromosome contains one very long, linear, double-stranded DNA molecule. A human chromosome's DNA can be several centimetres long if stretched out.
  • Histone proteins: small, positively charged proteins around which the negatively charged DNA is wrapped. Eight histones form a bead around which DNA wraps about twice, making a nucleosome; a string of nucleosomes coils further, then forms loops and coils, until the DNA is packed tens of thousands of times shorter than its stretched length. Histones allow the DNA to be packed into a small space, protect it, and control which genes can be accessed and transcribed.
  • Chromatids: after DNA replication, each chromosome consists of two identical sister chromatids. Each chromatid contains one DNA molecule, an exact copy of the other.
  • Centromere: the region where the two sister chromatids are held together. During mitosis, spindle microtubules attach at the centromere (via protein structures called kinetochores).
  • Telomeres: protective sections at each end of every chromatid, made of a short base sequence repeated many times (in humans, TTAGGG repeated hundreds to thousands of times). They do not code for proteins.
telomere centromere one chromatid sister chromatid telomere
A chromosome after DNA replication: two identical sister chromatids joined at the centromere, with telomeres (thick bars) at each end of each chromatid. Each chromatid is one DNA molecule wound around histone proteins.

How many chromosomes?

Each species has a characteristic number of chromosomes in its body cells: 46 in humans, 40 in mice, 14 in garden peas. Body cells are diploid (2n2n): they contain two sets of chromosomes, one set inherited from each parent. The two chromosomes of each matching pair are called homologous chromosomes: they have the same genes at the same positions (loci), though not necessarily the same alleles. So human body cells contain 23 homologous pairs. Gametes are haploid (nn, 23 in humans) and are made by meiosis, which is an A Level topic.

Key result

Counting chromosomes, chromatids and DNA molecules in a human body cell:

StageChromosomesChromatids per chromosomeDNA molecules
G146146
G2, prophase and metaphase46292
Anaphase (whole cell, after the chromatids separate)92192
Each daughter cell after cytokinesis46146

The number of chromosomes is counted by the number of centromeres. Once sister chromatids separate at anaphase, each one is called a chromosome.

The mitotic cell cycle

Definition

The cell cycle is the regular sequence of events that takes place between one cell division and the next. It has three main stages: interphase, mitosis (nuclear division) and cytokinesis (division of the cytoplasm).

y = 1 + min(max((x - 8)/8, 0), 1) - (1 + sign(x - 23))/2

(Horizontal axis: time / hours; vertical axis: mass of DNA per cell in arbitrary units. In G1 (0–8 h) the DNA content is constant at 1. During S phase (8–16 h) it doubles to 2 as DNA is replicated. It stays at 2 through G2 and mitosis, then halves back to 1 when the cell divides at cytokinesis (23 h), and the next cycle begins.)

Interphase

Interphase is the period between divisions. It is not a "resting" phase: the cell is very active, carrying out its normal functions and preparing to divide. It takes up most of the cycle, typically 90% or more of the time. It has three phases.

PhaseMain events
G1 (first gap or growth phase)The cell grows; it synthesises proteins (including enzymes needed for DNA replication) and makes new organelles such as mitochondria and ribosomes. The cell carries out its normal functions. A checkpoint at the end of G1 checks that the cell is large enough and the DNA is undamaged before committing to division.
S (synthesis phase)DNA replication: every DNA molecule is copied by semi-conservative replication, so each chromosome now consists of two identical sister chromatids joined at the centromere. Histone proteins are also made. The mass of DNA doubles.
G2 (second gap or growth phase)The cell grows further and makes proteins needed for division, such as tubulin for spindle microtubules. Energy stores (ATP) increase. In animal cells the centrioles have been duplicated. A checkpoint checks that DNA replication is complete and accurate.

Some cells leave the cycle after dividing and enter a non-dividing state called G0. Mature neurones and muscle cells stay in G0 permanently; liver cells can re-enter the cycle when the liver is damaged.

Mitosis

Mitosis is the division of the nucleus into two genetically identical nuclei. It has four stages, prophase, metaphase, anaphase and telophase, described in detail in Mitosis. Mitosis usually takes only a small fraction of the cycle (often around an hour in a 24-hour cycle).

Cytokinesis

Cytokinesis is the division of the cytoplasm to form two separate cells. In animal cells, the cell surface membrane is pulled inwards by a ring of protein filaments to form a cleavage furrow, which pinches the cell in two. In plant cells, vesicles from the Golgi body line up across the middle of the cell and fuse to form a cell plate, which becomes the new cell walls and membranes. Cytokinesis often begins during telophase.

Key result

The cell cycle in order: G1 → S → G2 → mitosis (prophase → metaphase → anaphase → telophase) → cytokinesis → G1 of the two daughter cells.

  • DNA replication happens in S phase of interphase, not during mitosis.
  • Growth happens in G1 and G2.
Chromosome counts (routine)

A cell from a plant has 24 chromosomes in G1.

(a) How many chromatids does it have in G1? (b) How many chromatids does it have in G2? (c) How many DNA molecules does each daughter cell receive after mitosis and cytokinesis? (d) The mass of DNA in the nucleus is 16 pg16\ \text{pg} in G1. What is it in G2 and in each daughter cell?

Solution

(a) 24: in G1 each chromosome is a single chromatid (one DNA molecule).

(b) 48: each of the 24 chromosomes has been replicated into two sister chromatids.

(c) 24: each daughter cell receives one chromatid of each chromosome, i.e. 24 DNA molecules.

(d) G2: 32 pg32\ \text{pg} (doubled in S phase). Each daughter cell: 16 pg16\ \text{pg} (the same as the parent cell in G1).

Time spent in each phase (moderate)

A student counted 400 cells in a root tip squash. The numbers in each stage were: interphase 352, prophase 20, metaphase 12, anaphase 6, telophase 10. The cell cycle in this tissue takes 20 hours.

Assuming the proportion of cells in a stage is proportional to the time spent in that stage, calculate the duration of interphase and of each stage of mitosis.

Solutiontime in stage=number of cells in stagetotal number of cells×length of cell cycle\text{time in stage} = \frac{\text{number of cells in stage}}{\text{total number of cells}} \times \text{length of cell cycle}
StageCellsProportionTime
Interphase352352/400=0.88352/400 = 0.880.88×20=17.6 h0.88 \times 20 = 17.6\ \text{h}
Prophase200.0500.0501.0 h=60 min1.0\ \text{h} = 60\ \text{min}
Metaphase120.0300.0300.6 h=36 min0.6\ \text{h} = 36\ \text{min}
Anaphase60.0150.0150.3 h=18 min0.3\ \text{h} = 18\ \text{min}
Telophase100.0250.0250.5 h=30 min0.5\ \text{h} = 30\ \text{min}

Check: 17.6+1.0+0.6+0.3+0.5=20.0 h17.6 + 1.0 + 0.6 + 0.3 + 0.5 = 20.0\ \text{h}. Interphase occupies 88% of the cycle; anaphase is the shortest stage.

The assumption is valid only if cells are dividing asynchronously (at random, not in step) so that a single snapshot reflects how long each stage lasts.

Telomeres

Every time a cell divides, all its DNA must be replicated. But the enzyme that copies DNA, DNA polymerase, cannot replicate the very end of a linear DNA molecule. (It can only add nucleotides to an existing strand, and on one strand at the end of the molecule there is nothing to start from; see DNA replication.) So at every replication, a short length of DNA is lost from the end of each new DNA molecule.

If genes were at the very ends of chromosomes, they would be progressively lost, and the cell would eventually lack essential genes. Telomeres solve this problem.

Key result

The role of telomeres

  • Telomeres are long, repetitive, non-coding base sequences at the ends of chromosomes.
  • Because DNA polymerase cannot copy the extreme end of a DNA molecule, a little DNA is lost from the end at each replication.
  • What is lost is part of the telomere, not part of a gene. Telomeres therefore prevent the loss of genes from the ends of chromosomes during DNA replication.
  • Telomeres also stop the ends of chromosomes from fusing with each other or being treated as broken DNA.

Telomeres get shorter with each division. When they become too short, the cell stops dividing (or dies). This limits the number of times most body cells can divide, roughly 50 times for human cells in culture.

Some cells make an enzyme, telomerase, which adds repeats back onto the telomeres, so they can divide indefinitely without losing genes. Telomerase is active in stem cells, in cells that produce gametes, and in most cancer cells, which is one reason cancer cells can divide without limit.

Telomere shortening (moderate)

A human cell has telomeres about 8000 base pairs long. About 80 base pairs are lost from each telomere at each division. The cell stops dividing when its telomeres are 4000 base pairs long.

(a) Calculate the number of divisions possible before the cell stops dividing. (b) Explain why the loss of these base pairs does not affect the proteins the cell makes. (c) Suggest why stem cells are able to divide many more times than this.

Solution

(a) Base pairs that can be lost =8000−4000=4000= 8000 - 4000 = 4000. Divisions =4000/80=50= 4000 / 80 = 50.

(b) The base pairs lost are part of the telomere, a repeated non-coding sequence; no genes are lost, so all polypeptides are still coded for.

(c) Stem cells produce telomerase, which adds repeats back to the ends of the telomeres after replication, so the telomeres do not shorten (or shorten much more slowly).

Exam-hard: interpreting a DNA content graph (6 marks)

A graph shows the mass of DNA in a cell over 30 hours. The mass is constant at 6.6 pg6.6\ \text{pg} from 0 to 8 h, rises steadily to 13.2 pg13.2\ \text{pg} between 8 and 16 h, stays at 13.2 pg13.2\ \text{pg} from 16 to 23 h, then falls suddenly to 6.6 pg6.6\ \text{pg} at 23 h.

(a) Name the phase of the cell cycle between 0 and 8 h, and describe two events that occur in it. (b) Explain the change between 8 and 16 h. (c) Explain why the DNA mass stays constant between 16 and 23 h, even though mitosis takes place during part of this time. (d) Explain the fall at 23 h.

Solution

(a) G1 (of interphase). Any two: cell growth; protein synthesis (e.g. of enzymes for DNA replication); replication of organelles (e.g. mitochondria); normal cell functions; checkpoint checks DNA before S phase.

(b) This is S phase: DNA replication (semi-conservative) takes place, so each chromosome becomes two sister chromatids; the mass of DNA doubles from 6.6 to 13.2 pg.

(c) This period includes G2 (growth, synthesis of spindle proteins) and mitosis. No DNA is made or lost: in mitosis the chromatids are separated into two nuclei, but they remain in the same cell until cytokinesis, so the mass per cell is unchanged.

(d) Cytokinesis: the cytoplasm divides and two daughter cells form, each receiving one complete set of chromosomes (one chromatid from each chromosome), so the DNA mass per cell halves back to 6.6 pg.

Watch out
  • DNA is replicated in S phase of interphase, not during prophase or mitosis. Saying "chromosomes replicate during prophase" is a classic lost mark.
  • Interphase is not a resting phase. The cell is growing, synthesising proteins and replicating DNA.
  • A chromosome is not always two chromatids. Before S phase it is a single DNA molecule; it has two chromatids only between S phase and anaphase.
  • Telomeres do not "stop DNA being lost". DNA is lost from the ends at each replication; telomeres ensure that what is lost is non-coding repeated sequence rather than genes.
  • Do not confuse centromere (where sister chromatids join) with centriole (an organelle that organises the spindle in animal cells) or centrosome.
Exam tip
  • The syllabus limits chromosome structure to: DNA, histone proteins, sister chromatids, centromere, telomeres. Learn a labelled sketch with all five.
  • When describing the cell cycle, name each phase and give a specific event: "G1: growth and protein synthesis; S: DNA replication; G2: further growth and synthesis of tubulin for the spindle; M: nuclear division; C: division of cytoplasm".
  • Time calculations: time=cells in stagetotal cells×cycle time\text{time} = \dfrac{\text{cells in stage}}{\text{total cells}} \times \text{cycle time}. Show the proportion and the multiplication, and convert to minutes if asked.
  • In telomere questions, the marking points are: DNA polymerase cannot replicate the end of the molecule; DNA shortens at each replication; telomeres are non-coding / repeated sequences; so genes are not lost.
Summary
  • A chromosome is a DNA molecule wound around histone proteins; after S phase it has two identical sister chromatids joined at the centromere, with telomeres at each end.
  • Human body cells are diploid with 46 chromosomes in 23 homologous pairs.
  • The cell cycle: interphase (G1, S, G2), mitosis, cytokinesis.
  • G1: growth and protein synthesis; S: DNA replication (DNA content doubles); G2: further growth, synthesis of spindle proteins.
  • Mitosis divides the nucleus; cytokinesis divides the cytoplasm (cleavage furrow in animals, cell plate in plants).
  • DNA polymerase cannot replicate the very end of a DNA molecule, so DNA is lost at each replication; telomeres are non-coding repeats that are lost instead of genes.
  • Telomerase in stem cells and cancer cells adds back telomere repeats.

Practice questions

Question
  1. Name the proteins around which DNA is wound in a chromosome, and state one function of them.
  2. State what is meant by a centromere.
  3. State what happens during S phase.
  4. A cell has 18 chromosomes in G1. State the number of chromatids at metaphase and the number of chromosomes in each daughter cell.
  5. Explain why a chromosome has two chromatids at the start of mitosis. (2 marks)
  6. Outline the events of interphase. (4 marks)
  7. In a sample of 250 cells, 30 were in mitosis. The cell cycle lasts 16 hours. Calculate the time spent in mitosis, in minutes.
  8. Distinguish between mitosis and cytokinesis.
  9. Outline the role of telomeres. (4 marks)
  10. Most cancer cells produce the enzyme telomerase, whereas most normal body cells do not. A drug that inhibits telomerase is being tested as an anticancer treatment. (a) Explain how the drug could stop cancer cells dividing indefinitely. (b) Suggest why the drug is likely to take many cell divisions before it has an effect. (c) Suggest one type of normal cell that might be harmed by the drug and explain why. (6 marks)
Answers
  1. Histones. Functions (any one): allow DNA to be coiled/packed into a small space; protect DNA; control access to genes for transcription.
  2. The region of a chromosome at which two sister chromatids are held together (and to which spindle microtubules attach during mitosis).
  3. DNA replication: every DNA molecule is copied (semi-conservatively), so each chromosome becomes two identical sister chromatids; histones are also synthesised.
  4. 36 chromatids at metaphase; 18 chromosomes in each daughter cell.
  5. DNA replicated during S phase (of interphase); each chromatid is one of the two identical DNA molecules produced, held together at the centromere.
  6. G1: cell grows, synthesises proteins (e.g. enzymes), organelles replicated; S: DNA replicated, histones made, chromosomes become two sister chromatids; G2: further growth, synthesis of proteins for division (e.g. tubulin for the spindle), energy stores increased, centrioles duplicated (animal cells); checkpoints check cell size and DNA before division.
  7. Proportion =30/250=0.12= 30/250 = 0.12; time =0.12×16=1.92 h=115 min= 0.12 \times 16 = 1.92\ \text{h} = 115\ \text{min} (115.2).
  8. Mitosis is the division of the nucleus into two genetically identical nuclei; cytokinesis is the division of the cytoplasm (and whole cell) into two cells, following mitosis.
  9. Telomeres are repeated, non-coding base sequences at the ends of chromosomes; DNA polymerase cannot replicate the very end of a DNA molecule, so the DNA shortens at each replication; the part lost is telomere rather than genes, so no genes are lost; telomeres also prevent chromosome ends fusing / being treated as damaged DNA.
  10. (a) Without telomerase, telomere repeats are no longer added; the telomeres shorten at every DNA replication; eventually they become critically short (or genes would be lost), so the cells stop dividing / die. (b) Cancer cells may start with long telomeres; only a small length is lost per division, so many divisions are needed before telomeres are short enough to stop division. (c) Stem cells (e.g. in bone marrow, or cells that produce gametes) use telomerase to keep dividing; inhibiting it would shorten their telomeres and limit their ability to replace cells such as blood cells.

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