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#error correction

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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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Replication Basics

Mismatch repair further improves fidelity after

Despite proofreading, occasional mismatches escape locking before next polymerization step. Post-replicative mismatch repair scans daughter strand discriminated in E. coli by transient hemimethylation of GATC sites remaining unmethylated for minutes. MutS protein detects backbone distortion caused by mismatch, MutL coordinates endonuclease MutH cleavage of unmethylated nascent strand, and helicase plus exonucleases remove error-containing segment. Resynthesis by Pol III restores correct sequence using parental strand template. This pathway improves fidelity additional 100 to 1000-fold and expl

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 5: Methyl-directed mismatch repair after replication

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