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DNA replication: Application AQA Biology Antiviral drugs Introduction The discovery of the structure of DNA in the 1950s was perhaps one of the landmark advances in biology in the last century. Once the structure had been worked out biologists rapidly began to explain how the molecule acts. Modern medical biologists recognise that a detailed understanding can help in developing effective drug treatments for a variety of diseases related to abnormalities in DNA function. Two common examples include cancer therapies and antiviral drugs. The aim of this task is to show how knowledge of DNA replication has been helpful in the development of the antiviral drugs used in the treatment of HIV/AIDS. Background In 1953 James Watson and Francis Crick published the structure of the DNA molecule. The structure of the molecule was shown to have two sugar phosphate backbones with base pairs between the backbones. This publication energised the scientific community. Armed with the knowledge of the structure of DNA biologists soon worked out how the molecule is copied in a process called DNA replication. This occurs during the ‘S’ phase of the cell cycle. The process relies on the complementary shapes of the free nucleotide bases pairing with the DNA template strand. The enzyme DNA polymerase plays a vital role in completing this process. In the 1980s cases of a deadly virus called human immunodeficiency virus (HIV) began to greatly increase. The virus caused damage to the body’s immune system leading to the onset of a condition called acquired immunodeficiency syndrome (AIDS). HIV infects one of the white blood cells called a Tlymphocyte. The virus has an RNA molecule as its genetic material. When it gets inside the lymphocyte it uses an enzyme it possesses called reverse transcriptase which causes the manufacture of DNA from the viral RNA. The virus then uses the copied DNA to make copies, using DNA polymerase, for the manufacture of new viruses. The medical community invested considerable time and money into researching a treatment or cure for this disease. One line of research was the development of antiviral drugs. The first relatively successful drug was called AZT (azidothymidine). This drug interfered with the manufacture of DNA. AZT is very similar in its structure to the nucleotide containing the base thymine. During the manufacture of a new DNA strand in DNA replication, normally a thymine containing nucleotide will pair up with an adenine base on the parent strand of DNA. Because of the very similar shape the AZT molecule can sometimes pair up instead of the thymine nucleotide. This stops the replication process, because it blocks the action of the enzyme controlling the process. This can happen to block the reverse transcriptase when it makes DNA from the RNA, or when DNA polymerase copies DNA. So both enzymes become inactive. By stopping the viral reproduction the drug slows the progress of the disease. © Oxford University Press 2015 www.oxfordsecondary.co.uk/acknowledgements This resource sheet may have been changed from the original 1 DNA replication: Application AQA Biology Task 1 2 Use your knowledge of DNA replication to create an annotated diagram to explain the process in normal healthy cells. Now show how the drug AZT might block the process in a second diagram. Questions 1 The diagram shows a short section of a DNA molecule. a b Name the parts labelled W, X, Y, and Z. (4 marks) Retro-viruses like HIV have RNA as their genetic material. This is converted into DNA. Give two differences in the structure of DNA and RNA. (2 marks) 2 DNA replication is the process where the DNA in the nucleus is copied. a At what stage in the cell cycle does DNA replication occur? b Apart from the DNA template, name two other things the cell needs for this process. c How does the cell ensure that it makes an exact copy of the DNA molecule? d The process of DNA replication is known as semi-conservative. Explain why. 3 (1 mark) (2 marks) (2 marks) (2 marks) An anti-viral drug called azidothymidine (AZT) is used to treat viral infections like HIV. It acts by disrupting DNA replication. The AZT molecule has a similar shape to part of the nucleotide containing the base thymine. a b c d State two differences between these two molecules. (2 marks) Suggest how the AZT molecule might become incorporated into the DNA during replication. (2 marks) Suggest how the AZT molecule might halt or disrupt the DNA replication process. (1 mark) How might this be useful as an antiviral treatment? (1 mark) © Oxford University Press 2015 www.oxfordsecondary.co.uk/acknowledgements This resource sheet may have been changed from the original 2