Practice question

DNA replication fidelity arises from sequential error control. Base selection by polymerase active site contributes 10^4 to 10^5 discrimination, but misincorporation still 10^-4 to 10^-5. Intrinsic 3' to 5' exonuclease proofreading removes ~90-99% of misinserted nucleotides, increasing accuracy additional hundredfold, dropping error rate to about 10^-7. Subsequent mismatch repair scanning newly replicated strand improves further thousandfold to 10^-10. Thus proofreading accounts for approximately two orders magnitude improvement. Without exonuclease, mutator phenotype observed, leading to increased spontaneous mutations and cancer predisposition, illustrating quantitative importance of editing.