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IN DEPTH 3.2 DNA – A GORDIAN KNOT

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At the start of his career Alexander the Great was shown the Gordian Knot, a tangled ball of knotted rope, and told that whoever untied the knot would conquer Asia. Alexander cut through the knot with his sword. A similar problem occurs in the nucleus, where the 46 chromosomes form 2 m of tangled, knotted DNA. How does the DNA ever untangle at mitosis? The cell adopts Alexander's solution – it cuts the rope. At any place where the DNA helix is under strain, for instance, where two chromosomes press against each other, an enzyme called topoisomerase II cuts one chromosome double helix so that the other can pass through the gap. Then, surpassing Alexander, the enzyme rejoins the cut ends. Topoisomerases are active all the time in the nucleus, relieving any strain that develops in the tangled mass of DNA.

Concerns that a terrorist organization might release large amounts of anthrax spores have caused several governments to stockpile large amounts of the antibiotic Cipro. This works by inhibiting the prokaryotic form of topoisomerase II (sometimes called gyrase) hence preventing cell replication.

Figure 3.6. A spread of human chromosomes (at metaphase – see page 236). The red dots (generated using a technique called fluorescence in‐situ hybridization or FISH) reveals the COL1A1 gene which codes for collagen 1A1 (see Medical Relevance 3.2 on page 47).

Source: Image by Mariano Rocchi, Resources for Molecular Cytogenetics, Department of Biology, University of Bari. Reproduced by permission.

Cell Biology

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