Mitotic Cell Cycle

1. The Mitotic Cell Cycle — Overview

A cell is the basic unit of life and, like an organism, has a life cycle. It is divided into phases: G₁ → S → G₂ → M (mitosis). G₁ + S + G₂ together = INTERPHASE.

Mitosis = nuclear division (1 nucleus → 2 genetically identical nuclei). Cytokinesis = cytoplasm division (→ 2 separate daughter cells). Together = cell division.

Human cell: 46 chromosomes (23 pairs). For the chromosome number to be preserved in every division, the DNA must replicate first (46 → 92 DNA strands) and then be shared out 46 + 46.

What happens during interphase

1. Organelle synthesis
2. Synthesis of proteins, carbohydrates and lipids
3. Metabolic reactions
4. DNA replication (S phase) — and just before mitosis the centrosome duplicates (see §6)

2. Diploid (2n) vs Haploid (n) Cells

	Diploid (2n)	Haploid (n)
Chromosome sets	2 complete sets	only 1 set
Formed by	result of mitosis	result of meiosis
Cell type	somatic cells	germ cells → gametes (sperm, egg)
In humans	2n = 46 chromosomes	n = 23 chromosomes

Each pair of chromosomes = one from father (F) + one from mother (M). Zygote = n + n = 2n.

3. Chromosome · Chromatin · Chromatid

Chromatin: DNA wrapped (coiled) around histone proteins — the thread-like, loosely coiled form seen in interphase; individual chromosomes can’t be seen separately.

Chromosome: the condensed form of DNA/chromatin — shortened, thickened, clearly visible (during mitosis).

Chromatid: one of the 2 identical parts of a replicated chromosome, held together by a centromere.

Nucleosome: a section of DNA wrapped around 8 histone proteins (protein core). Not the same as chromatin (= DNA + histones overall). Not needed in depth for AS, but may appear in Paper 2 case studies.

Chromatin = coiled, thread-like, chromosomes not distinct. Chromosome = condensed, distinct, X-shaped (if replicated). Both exist in the nucleus.

• Centromere: the common point joining the two sister chromatids. Need not be in the exact middle — different chromosomes have it in different positions (long/short arm — no need to learn).
• Sister chromatids: genetically identical = same DNA length, share a centromere, same genes (gene A opposite gene A …). Formed by DNA replication.
• Telomere: cap at the ends of the chromatids (see §12).
• One DNA molecule = one chromosome (whether 1 or 2 chromatids).

4. Chromosome Number vs DNA-strand Number

Chromosome number is constant (46) at any time of the cycle in a human body cell. Only the number of DNA molecules changes. After the S phase, 92 strands exist but they are joined in pairs ⇒ still 46 chromosomes.

• A (46 → 92): DNA replication = S phase. Must happen before mitosis.
• B (92 → 46): nuclear division finishes (end of mitosis) — halving by division, not by chromatid breaking (breaking would not change the strand count).

Quick revision flow: interphase cell (46 chr) → DNA replication (92 DNA strands, 46 chr) → mitosis (two nuclei, 46 each) → cytokinesis (two cells, 46 each).

5. Homologous Chromosomes

Definition: a pair of chromosomes with the same length, the same position of centromere and the same genes at the same positions (loci).

• The genes can, however, have different alleles (G vs g).
• One chromosome comes from the mother, the other from the father.
• 23 homologous pairs in humans = 46 chromosomes.

6. Cell Structures Involved in Mitosis

• Centrosome = the most common MTOC (microtubule organising centre). Contains a pair of centrioles lying at 90° to each other.
• Centriole = hollow cylinder built of 9 microtubule triplets (3 microtubules each). Present in animal cells only.
• Plant cells do mitosis too, but have no centrioles — microtubules organise the spindle by another route.

Just before mitosis, during interphase, the centrosome divides itself ⇒ 2 centrosomes = 2 pairs of centrioles (4 centrioles in total). In prophase they move to opposite poles; being made of microtubules, they give rise to the spindle fibres (microtubules).

7. Mitosis — The Four Stages (PMAT)

Definition: mitosis is a form of nuclear division which produces genetically identical daughter cells. Occurs in 4 stages:

Before prophase: DNA replicated (S) + centrosome duplicated (interphase). The spindle (made of microtubules from the centrioles) is what the whole of mitosis is based on.

① Prophase

1. Condensation of chromosomes: chromatin shortens & thickens ⇒ chromosomes become distinctly visible (same thing as “DNA coils into sister chromatids”).
2. Nuclear envelope (double membrane) disintegrates — the 1.8 m DNA can’t fit in a 6 µm nucleus once condensed, so chromosomes lie free in the cell.
3. Nucleolus disappears.
4. Centrosomes migrate to the opposite poles.
5. Spindle forms — centrioles’ microtubules organise into spindle fibres. At the end of prophase the spindle is complete but chromosomes are not yet attached.

② Metaphase

1. Chromosomes attach themselves to spindle fibres via kinetochores — special protein “glue” at the edges of the centromere (part of the centromere, not the whole of it; like dots of glue).
2. Chromosomes align at the equator of the spindle (imaginary line halving the cell).

③ Anaphase

1. The centromere divides (the sister chromatids themselves don’t divide) ⇒ the sister chromatids are separated.
2. Separated chromatids move to opposite poles, centromere leading (seen under light microscope: V-shapes pointing at the poles). Movement is due to contraction (shortening) of the spindle microtubules.
3. Chromatids detach from spindle fibres at the end of anaphase.

④ Telophase

Reverse of prophase:

1. Chromosomes decondense back into chromatin.
2. Nucleolus reappears.
3. Nuclear envelope reforms around each set.
4. Cell now has 2 genetically identical nuclei (cytokinesis not yet done; 92 chromosomes in the one cell, 46 per nucleus).

Stage	Key events
Prophase	chromosomes condense · envelope breaks · nucleolus gone · centrosomes → poles · spindle forms
Metaphase	attach via kinetochores · align at equator
Anaphase	centromere splits · chromatids pulled to poles, centromere first · microtubules contract
Telophase	decondense · nucleolus back · envelope reforms · 2 identical nuclei

8. Significance of Mitosis

1. Asexual reproduction (genetically identical offspring)
2. Tissue repair (e.g. skin cells replace themselves after a cut)
3. Tissue growth
4. Plays a vital role in immune responses (cells multiply)
5. Development of tumours (when mitosis goes uncontrolled)

Every cell has a mitotic cycle; a worn-out heart/muscle/skin cell is replaced by a genetically identical, already-specialised cell made by mitosis.

9. Cytokinesis — Splitting the Cytoplasm

After telophase there is one cell with two nuclei. Cytokinesis divides the cytoplasm and organelles (shared between the two cells) ⇒ 2 genetically identical daughter cells. It happens differently in animal and plant cells.

In animal cells — formation of a cleavage furrow

1. A ring of microfilaments appears around the equator of the cell.
2. The ring constricts (tightens, diameter narrows) to create a cleavage furrow, which deepens.
3. The cell eventually pinches off into 2 daughter cells.
4. Cytoplasm and organelles are shared between the 2 cells.

Main observable feature = cleavage furrow. (Animal cells have no cell wall, only a cell membrane; irregular shape is restored by the cytoskeleton.)

In plant cells — formation of a cell plate

1. Microtubules move “carbohydrate-rich” Golgi vesicles towards the midline (equator) of the cell.
2. Golgi vesicles fuse to form the cell plate.
3. Carbohydrates (cellulose, a β-glucose polysaccharide) are deposited onto the cell plate to form the mature cell wall.
4. Cytoplasm and organelles are divided between the new cells.

10. Types of Cell in the Human Body

Somatic cells	Germ cells	Stem cells
All cells other than germ and stem cells (skin, heart, muscle…). Divide by mitosis; diploid.	Can divide by mitosis AND meiosis — the only cells that undergo meiosis. Give rise to gametes: sperm (n) & ovum (n). Found in gonads: testes (♂), ovary (♀). The germ cells themselves are diploid (2n).	Can divide and differentiate to produce other cell types (via mitosis — chromosome number preserved). Limited in number. Have active telomerase.

Analogy: a plant’s stem gives rise to different branches, so a stem cell gives rise to different cell types. Why stem cells divide by mitosis: a stem cell is 2n and the RBC/WBC it makes is also 2n — chromosome number preserved = mitosis.

11. Stem Cells, Potency & Differentiation

Differentiation: process of cell specialisation — an unspecialised cell takes on a designated, specialised role (like a doctor specialising after MBBS).

Potency: the ability of stem cells to divide and differentiate to produce other cell types (“how powerful”: totipotent = toti ≈ total, pluripotent = plural = many, multipotent = some).

Type	Can produce	Example	When
Totipotent	ANY cell type	Zygote	before birth
Pluripotent	MANY cell types	Embryonic stem cells	before birth
Multipotent	SOME cell types	Bone-marrow stem cells (→ RBCs, WBCs…)	after birth

• Zygote = fertilised cell (n + n = 2n), not specialised; divides → 8, 16, 32 cells → embryo (first ~10 weeks; implants in uterus) → fetus. It makes every cell type and organ.
• Multipotent cells replace worn-out cells after birth — e.g. RBC lifespan ≈ 120 days (~3–4 months) so bone-marrow stem cells keep making blood cells for life (this is why bone-marrow transplants are used in blood diseases).

1. Stem cell divides by mitosis → 2 genetically identical (undifferentiated) daughter cells.
2. One differentiates into a specialised cell (e.g. muscle — long multinucleate cylinder, squamous — flat (gas exchange), columnar — column shape, RBC…).
3. The other replaces the parent stem cell — otherwise stem cells would run out (they’re limited, and only stem cells can differentiate).

12. Telomeres & Telomerase

Telomeres: non-coding, repetitive sequences of DNA nucleotides found at the ends of the chromatids — like the plastic cap on a shoelace or the cap on a toothpaste tube: they protect the DNA.

End replication problem

Definition: a small part of the ends of the DNA molecule is lost each time DNA replicates (ends of linear DNA can’t be copied completely — like a photocopier missing the last line). Could lead to loss of essential genes — which the telomeres prevent.

• Only linear DNA (eukaryotes) has this problem. Circular DNA (bacteria, mitochondria, chloroplasts) has no ends ⇒ no end replication problem.
• Telomeres are “sacrificed” instead of genes: they shorten each time the DNA replicates.
• A cell stops dividing once the telomeres are finished (else genes would be lost). That’s the end of that cell line.

Telomerase is an enzyme which lengthens the telomeres upon each replication (adds back the lost non-coding nucleotides — like writing in the missing last line with a pen).

Why stem cells need telomerase: they must never stop dividing (division comes first, then differentiation, and they’re limited in number) for the whole life. Eg: if telomeres = 17 cm and 1 cm lost per division ⇒ only 17 divisions — then no more blood cells! Telomerase keeps their length constant.

13. Tumours & Formation of a Tumour

An abnormal irregular mass of cells from uncontrolled mitosis. Two types: Benign (harmless, not spreading — not called cancer; usually no chemo/radiation) and Malignant = cancerous (harmful, spreads). A tumour is, strictly, a malignant mass. Doctors take a small sample to a lab to decide benign vs malignant.

1. Mutation in the genes that control cell division (cancer needs a non-silent mutation):
   • Proto-oncogene: normally inactive in body cells, but becomes active due to mutation (= oncogene) and can cause cancer. Proto-oncogene = inactive form; oncogene = active form.
   • Tumour suppressor gene: normally active in body cells (a protective “guard” suppressing tumours) but becomes inactive due to mutation ⇒ tumour formation.
2. Uncontrolled mitosis — cells divide repeatedly, cell-cycle checkpoints not controlled; divide rapidly and indefinitely because telomerase becomes active, and have a shorter interphase.
3. Irregular mass formed = primary growth (localised, in one region — can be removed by surgery).
4. Body defends: immune attack and apoptosis (programmed cell death — cells “suicide”).
5. Cells that escape immune attack and fail to undergo apoptosis develop their own blood supply and lymphatic system (nutrients + hijacked transport route).
6. Cancerous cells spread to other parts of the body (apart from the primary site) via blood/lymph and grow at those sites = secondary growth. The spreading is called METASTASIS.

14. Mutagens & Carcinogens

Mutagen: a substance that causes mutation.
Carcinogen: a mutagen that can cause cancer (mutation in a cell-division gene). So every carcinogen is a mutagen (subset).

Examples of mutagens:

1. Ionising radiation (X-rays, γ-rays)
2. UV light
3. Free radicals
4. Chemicals — tar, alcohol etc. (tobacco, alcohol)
5. Viruses & bacteria — e.g. HIV; H. pylori (certain ones can alter DNA)

Other factors that cause or increase the risk of cancer

• Hereditary factors (inherit a mutated cancer gene — family history, e.g. breast cancer; may never be expressed) — not a mutagen because no substance caused a mutation in that person.
• Occupational exposure (e.g. working near nuclear radiation)
• Obesity
• Smoking & drinking (also diet / lifestyle)

15. Mitosis vs Meiosis

Mitosis	Meiosis
Produces genetically identical daughter cells	May lead to genetic variation
Conserves chromosomal number (2n → 2n)	Halves chromosomal number (2n → n)
Produces 2 daughter cells	Produces 4 haploid cells
Allows asexual reproduction	Allows sexual reproduction
Haploid and diploid cells can undergo mitosis	Only diploid germ cells can undergo meiosis

16. Full Chapter Cheat-Sheet