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#fidelity

2 public questions tagged with this topic.

High fidelity of translation depends mainly on

High translational fidelity, error rate about 1 in 10000 codons, depends principally on aminoacyl-tRNA synthetases employing double-sieve and proofreading mechanisms. Initial activation selects amino acids by size and chemistry in synthetic active site, hydrolyzing non-cognate adenylates, while separate editing domains hydrolyze misacylated tRNAs after transfer. Without this upstream editing, ribosome would insert wrong residues despite codon-anticodon correctness. Ribosome contributes kinetic proofreading at decoding, but ultimate assignment of amino acid to anticodon is dictated by synthetas

Ref: Berg et al., Biochemistry, 9th ed., Chapter 32, Aminoacyl-tRNA synthetase proofreading ensures translational fidelity

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