34 - Bases may take on rare tautomeric forms prone to...

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Bases may take on rare tautomeric forms prone to mismatch 1
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Proofreading removes mispaired bases 2 Why do viruses mutate so quickly?
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Proteins at work at the replication fork 3
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The mechanics of DNA replication - unwind the double helix (Helicase) - reduce tension introduced by unwinding (Gyrase) - start strand synthesis (Primase) - synthesize (DNA polymerase III) - remove RNA primer (DNA polymerase I) - link newly synthesized strands (ligase) Klug, 10th, Figure 11.13 4
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Origins of replication Replication begins at specific sites (origins of replication). Replication forks proceed in both directions. 5
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Bacterial chromosomes oriC ter Bacterial chromosomes are circular and have a single origin of replication ( oriC ). DNA synthesis proceeds in both directions. 6
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DNA replication proceeds in two directions 7
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The replication problem at chromosome ends ( telomeres ) Each Okazaki fragment of the lagging strands needs a primer. At the very end of the chromosome the RNA primer cannot be replaced by DNA. Consequence: the chromosome would get shorter with each round of DNA replication. 8
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Telomere lengthening Telomerase carries a short RNA molecule (red letters) that acts as a template for the addition of a complementary DNA sequence (blue letters). Telomeres are short repetitive sequences at the end of a chromosome (e.g., TTGGGG). 9
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Telomere lengthening Primase, DNA polymerase and ligase can now fill the original gap. This still will leave a gap at the very end, but the gap is now within the repetitive telomere sequence, which can be replaced at any time by the telomerase. 10
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Werner syndrome causes premature aging due to a defective WRN gene involved in telomere cap structure. They have shorter telomeres than normal people. Germ cells produce ample telomerase, but somatic cells produce very little or none. Hence, the chromosomes of proliferating somatic cells get progressively shorter with each cell division until the cell stops dividing. There may be a link between telomere shortening and aging. Most cancerous somatic cells have telomerase activity and can remain ‘immortal’ in cell cultures. 11 Note: Here ‘germ’ cell = gametes; somatic cells = body cells (some of which are capable of divisions)
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RNA polymerase in action Chapter 8 RNA: Transcription and processing 12
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Genotype to phenotype genotype phenotype Klug, 10th, Figure 13.1 Messenger RNA (mRNA) Primary RNA transcript 13
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