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3.3 DNA replication

Figure Q3.12 Possible density gradient patterns of DNA after bacteria are transferred from 15 N- to 14 N containing medium and allowed to undergo three subsequent rounds of replication. Distance along the horizontal axis reflects the weight of the DNA, with the lightest DNA on the left and the heaviest on the right. The area under the curve is a measure of the amount of double-stranded DNA with a particular composition of 15 N- and 14 N-labelled chains.

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13. The enzymes topoisomerase and telomerase have both been pro posed as targets for anti-cancer drugs. What is the role of each of these enzymes in DNA replication, and why might inhibiting their activity be therapeutic strategies to treat cancer? 14. It is often suggested that the size of the genome reflects the com plexity of the organism. Discuss this with reference to the data in

Table 3.2 that gives the genome sizes and gene numbers of humans and the nematode worm, Caenorhabditis elegans . 15. The genetic disease xeroderma pigmentosum (XP) is caused by defects in proteins required for NER. People with XP suffer from skin cancer caused by exposure to sunlight. Outline the chain of events within skin cells that leads to cancer in these individuals.

FURTHER READING

An exploration of the impact of the human genome sequence in the decade a er its publication, and the road ahead in ful lling the promise of genomics for medicine. Fuss, J. O. & Cooper, P. K. (2006) DNA repair: dynamic defenders against cancer and aging. PLoS Biol . 4 : e203. https://doi.org/10.1371/journal. pbio.0040203 An accessible summary of DNA repair mechanisms focusing on humans and the consequences of defects in repair systems. Levy, S.B. (1998) e challenge of antibiotic resistance. Sci. Am. 278 : 46–53. doi: 10.1038/scienti camerican0398-46. While this is an older article, it clearly sets out the challenges posed by antibi otic resistance in accessible language.

Chambers, D. A., Reid, K. B. M., & Cohen, R. L. (1994). DNA: the double helix and the biomedical revolution at 40 years. FASEB J. , 8 : 1219–26. Reviews a meeting to mark the 40th anniversary of the double helix. Despite being somewhat out of date it provides a good overview of work that followed on from the publication of the structure of DNA. Hanawalt, P. C. (2004) Density matters: the semiconservative replication of DNA. Proc Natl Acad Sci USA 101 : 17889–94. A perspective piece on the elegant original experiments that demonstrated that DNA replication is semiconservative, and some of the follow up. Lander, E. S. (2011) Initial impact of the sequencing of the human genome. Nature 470 : 187–97.

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