Replication and division of nuclei and cells

Syllabus points

• Describe the cell cycle, including interphase, mitosis and cytokinesis.
• Explain the significance of mitosis in growth, repair and asexual reproduction.
• Outline the role of telomeres and of stem cells.
• Explain how uncontrolled cell division leads to cancer.

The cell cycle

The cell cycle is the sequence a cell goes through from one division to the next. It has two parts of very unequal length.

Interphase takes up around 90 per cent of the cycle. It is not a resting stage, whatever the name suggests, and calling it one costs marks. It divides into three:

• G1: the cell grows, makes proteins and organelles, and the number of mitochondria and ribosomes increases.
• S (synthesis): DNA replication. Each chromosome is copied, so afterwards it consists of two identical sister chromatids joined at a centromere. The amount of DNA in the nucleus doubles.
• G2: further growth, and the cell checks the replicated DNA for errors before committing to division.

The mitotic phase is mitosis, the division of the nucleus, followed by cytokinesis, the division of the cytoplasm.

The DNA quantity question

Cambridge asks this constantly, so it is worth being exact.

The chromosome number does not change during S phase. A chromosome with two chromatids is still one chromosome. The DNA quantity doubles, and it halves again at anaphase when the chromatids separate.

If a question gives a mass of DNA rather than a count, the same logic applies: a cell with 1.2 units in G1 has 2.4 at the end of S and 2.4 through G2.

Checkpoints

The cycle is controlled at checkpoints, where the cell will not proceed unless conditions are right.

• The G1 checkpoint confirms the cell is large enough, has enough nutrients, and that the DNA is undamaged. A cell that fails may enter G0, a non-dividing state, which is where most specialised cells such as neurones spend their lives.
• The G2 checkpoint confirms DNA replication finished correctly.
• The metaphase checkpoint confirms every chromosome is attached to the spindle before the chromatids are pulled apart.

Checkpoints exist because an error copied into every descendant cell is far more costly than a delay.

Why mitosis matters

Mitosis produces two nuclei that are genetically identical to each other and to the parent nucleus, with the same number of chromosomes.

That matters for:

• Growth, in a multicellular organism, from a zygote to an adult.
• Repair and replacement of damaged or worn cells. Human red blood cells last about 120 days and skin is replaced continuously.
• Asexual reproduction, where the offspring are clones of the parent. Bacteria use binary fission rather than mitosis, but many plants, fungi and simple animals use mitosis directly.
• Immune response, where a selected lymphocyte divides by mitosis to produce a clone of cells that all recognise the same antigen. That is topic 11.1.

Genetic identity is the point of the whole process. A skin cell replacing another skin cell would be no use if it carried a different set of genes.

Telomeres

The ends of a chromosome are capped by telomeres, repeating non-coding DNA sequences.

DNA polymerase cannot copy right to the very end of a DNA molecule, so a short length is lost at each replication. Telomeres exist so that what is lost is repeated non-coding sequence rather than a gene.

Because a little goes each time, telomeres shorten with every division. When they become too short the cell can no longer divide safely, and it stops. This puts a limit on the number of divisions a normal body cell can make, and links to ageing.

Telomerase is the enzyme that rebuilds telomeres. It is active in stem cells and in the cells that produce gametes, which is why those can divide many times. In most body cells it is switched off. In cancer cells it is frequently switched back on, which is part of how a tumour keeps dividing indefinitely.

The direction of that relationship is a common trap: a high concentration of telomerase means more divisions, not fewer.

Stem cells

A stem cell is an unspecialised cell that can divide repeatedly and can differentiate into one or more specialised types.

• Totipotent cells can produce every cell type including the placenta. Only the zygote and the cells of the very early embryo are totipotent.
• Pluripotent cells can produce almost any body cell type but not a whole organism. Embryonic stem cells are pluripotent.
• Multipotent cells produce a limited range. Bone marrow stem cells produce the various blood cells.

Plant stem cells sit in meristems, at root and shoot tips and in the cambium, and remain able to divide throughout the plant's life.

Every cell in an organism carries the same genes. What makes a liver cell different from a nerve cell is which genes are expressed, and differentiation is the process of switching some on and others off permanently.

Cancer

Cancer is uncontrolled cell division. A cell that ignores the checkpoints divides when it should not, and the descendants form a tumour.

The cause is a mutation, a change in the DNA base sequence, in genes that control the cell cycle. Two classes matter:

• Proto-oncogenes normally stimulate division. A mutation can turn one into an oncogene that stimulates division continuously.
• Tumour suppressor genes normally halt division. A mutation that stops one working removes the brake.

Usually several mutations are needed in the same cell line, which is why cancer becomes more common with age.

A benign tumour stays in one place and is often harmless. A malignant tumour invades surrounding tissue and cells may break away and travel in the blood or lymph to form secondary tumours elsewhere, which is metastasis.

Anything that increases the mutation rate raises the risk. Mutagens include ionising radiation, ultraviolet light, and chemical carcinogens such as those in tobacco smoke. Some mutations are inherited, which is why certain cancers run in families.

Common mistakes

• Calling interphase a resting stage. It is the longest and most active part of the cycle.
• Saying the chromosome number doubles in S phase. The DNA quantity doubles; the chromosome number does not.
• Saying telomeres stop the chromosome fraying. They exist so that the DNA lost at replication is non-coding.
• Saying high telomerase limits division. It allows more division.
• Saying cancer is caused by one mutation. Usually several are needed in the same cell line.