Lecture 22. Tuesday, November 21. DNA basepairing specificity

Lecture 22. Tuesday, November 21. DNA basepairing specificity

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Restricted: For students enrolled in Chem130/MCB100A, UC Berkeley, Fall 2006 ONLY 1 John Kuriyan: University of California, Berkeley Chem C130/MCB 100A, Fall 2006, Lecture 22 Stability of DNA basepairing. DNA polymerase make 1 error in 10 7 –10 8 in corporations of nucleotide. What would be the relative binding free energy of nucleotides to the template to account for this difference?
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Restricted: For students enrolled in Chem130/MCB100A, UC Berkeley, Fall 2006 ONLY 2 We can write a thermodynamic cycle as follows: Because this is a cycle, Δ G c w = Δ G w − Δ G c = ΔΔ G w , c Δ G c w = -RT ln K where K = PT i dN w TP [ ] dN c TP PT i dN c TP [ ] dN w TP If we assume that the nucleotide concentrations are high, then
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3 dN c TP dN w TP and so: K = PT i dN w TP [ ] PT i dN c TP [ ] Conceptually, we can relate K to the fidelity. If the error rate is 10 -7 , then K 10 -7 Δ G c w = -RT ln K 40 kJ mol -1 Conclusion: If wrong base pairs are destabilized by ~ 40 kJ mol -1 with respect to correct base pairs then replication fidelity could be explained. How do we determine the values of
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Lecture 22. Tuesday, November 21. DNA basepairing specificity

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