MCELLBI 110 Lecture Notes - Lecture 10: Dna Mismatch Repair, Dna Replication, Muts-1

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Factors influencing fidelity: accuracy of template cognate dntp selection: the frequency of incorporation of an incorrect nucleotide depends on, 1. Dna polymerase active site discrimination/quality control processes: rejection of rntps, check the fit assessment of proper base pairing, minor groove tracking to monitor product is b form, 2. Proof reading 3"-5" exonuclease activity of replicative polymerase. Potential impediments to replication fork progress: dna replication stress. In e. coli transient hemi-methylated state after dna replication is what distinguishes the parental (methylated, correct) strand from newly made (unmethylated, incorrect) strand. How muts discriminates a mismatch: muts dimer scands dsdna sensing a mismatch by trying to bend it. Muts inserts a phenylalanine side chain into a base stacking position, which stabilizes the kink and allows the next steps in mismatch repair. Eukaryotic mutl itself has endonuclease activity: mammalian muts proteins are heterodimers with distinct functions, only one subunit binds the mismatch or loop.

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