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#replication fidelity

2 public questions tagged with this topic.

Repair Pathway

Proofreading increases replication fidelity approximately by

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 incr

Ref: Watson et al., Molecular Biology of the Gene, 7th ed., Chapter 10: Quantitative Contribution of Proofreading 100-fold

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Repair Pathway

Proofreading during DNA replication involves which activity of DNA polymerase?

Replicative DNA polymerases such as Pol delta and Pol epsilon possess intrinsic 3' to 5' exonuclease domain distinct from polymerase active site. When incorrect nucleotide incorporated, duplex fraying moves primer terminus from polymerase to exonuclease site, hydrolyzing mispaired nucleotide before next incorporation. This proofreading activity is intrinsic exonuclease not 5' to 3' activity associated with removal of primers like Pol I. Endonuclease cleavage at internal sites and ligase activity sealing nicks are different repair steps unrelated to immediate correction during chain elongation,

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 5: Proofreading 3' to 5' Exonuclease Activity

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