Topic 15 & 16, DNA damage & repair

Topic 15 & 16, DNA damage & repair - Topics...

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Topics 15/16: DNA damage and repair
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Learning Objectives: Topic 15 Be able to define the following terms: error rate, proofreading, mutagen, hydrolytic cleavage, alkylation, mismatch, transposable element, retrovirus Be able to list environmental mutagens that can cause DNA damage and types of damage caused Be able to explain how a DNA base can be changed to a different DNA base through DNA damage (slide 15) Be able to explain the cellular consequences of different types of DNA damage
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Errors introduced by DNA polymerase during DNA replication Error rate of DNA polymerase is pretty low (1 in 10 4 to 10 5 nucleotides) Proofreading by DNA polymerase corrects 99- 99.9% of it’s own mistakes Mismatch DNA repair corrects another 99-99.9% of errors/mutations Sum total: permanent errors occur every 1 in 10 8 to 10 11 bp, and our genome size is 6x10 9 bp of DNA per diploid cell
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Environmental conditions that can cause DNA damage Mutagen (something that causes mutations): UV light X-rays Gamma rays Hydrolytic cleavage from water Oxidation (free radicals) Alkylating agents Chemical cross-linking agents How we get exposed to it: Sunlight Outer space (or the dentist) Outer space, radioactive isotopes Water present in cells Normal cellular processes Natural & synthetic chemicals
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Types of DNA damage Type of damage Pyrimidine dimers (intra-strand crosslinks) Hydrolytic cleavage Depurination (loss of purine base) Deamination Alkylation Addition of –OH or =O to bases Inter-strand crosslinks Double-strand breaks DNA insertions Cause of damage UV light Water Water Water Enzymes add alkyls Reactive oxygen species Mustard gas X-rays, gamma rays Viruses
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Consequences of DNA damage: how to think about it Will the mistake result in a change in the phenotype of the organism? Why or why not? Will the mistake be passed on to the next generation? What would happen if DNA replication or RNA transcription machinery encountered a particular type of damage? Would progress be halted? Would that machinery detect the mistake? Which DNA strand is wrong and which is right? Could the machinery fix the mistake?
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An example of intra-strand DNA damage (within the same strand) --Bond formed between two bases on same strand UV light can cause destabilization of chemical bonds. As bonds re-form, they may assume an improper configuration. 2 different possible products, depending upon where bonds form. Both types of products are examples of DNA damage Pyrimidine dimers can form when DNA is exposed to UV light Aka, dimers Aka, photoproducts
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Pyrimidine dimers can form when DNA is exposed to UV light Figure 10.01a: Cyclobutane pyrimidine dimer Adapted from Friedberg, E. C., et al. DNA Repair and Mutagenesis, 2/3. ASM Press, 2005.
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Topic 15 & 16, DNA damage & repair - Topics...

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