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BSCI DNA Repair - The Basic Problem DNA Damage S phase G1...

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The Basic Problem S phase Mitosis G2 G1 DNA Damage DNA Damage
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Magnitude of Mutation Problem Spontaneous mutation rate = 1 per 10 9 bases per cell division Number of bases in mammalian genome = > 10 9 Number of mutations = 1 per genome per cell division Number of cell divisions = 10 7 per second You’ll suffer 72 billion mutations during this lecture
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Mitigating factors Most of DNA is non-coding (less than 2% of human genome contains informative information) Most mutations are inconsequential Mutations that do cause a cellular defect will most likely kill the cell so will typically not cause diseases such as cancer
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For example: Relevant targets for cancer: approximately 200 genes Average size of a gene coding sequence, splice sites, and key regulatory regions is approximately 2500-5000 base pairs So target size in genome for mutations for cancer is approx. 5 x 10 5 bases. So 5 x 10 5 relevant bases/6 x10 9 total bases means that each mutation per cell division only has a 0.008% chance of hitting a cancer gene.
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Is 0.008% a large risk or small risk? Assume 4 x 10 9 proliferating stem cells So this means that 320,000 stem cells get a mutation in a cancer gene each time it divides.
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