misincorporate

Misincorporation refers to the erroneous insertion of an incorrect nucleotide or amino acid during the synthesis of a nucleic acid or protein. In molecular biology, misincorporation most commonly describes mistakes that occur during DNA replication, transcription, or translation, and that can alter genetic information or protein sequences if not corrected.

During DNA replication, DNA polymerases add nucleotides opposite the template strand. Incorrect pairing constitutes misincorporation. Fidelity is enhanced by the polymerase’s proofreading exonuclease activity and by post-replicative mismatch repair systems that detect and correct mispaired bases. Without proofreading and repair, the initial error rate is roughly 10^-4 to 10^-5 per nucleotide; these safeguards reduce the rate by several orders of magnitude, making most misincorporations harmless or removable.

RNA synthesis by RNA polymerases also involves misincorporation, though at lower fidelity than DNA replication. Errors in RNA are not heritable but can affect the resulting transcripts and, if translated, the produced proteins. In translation, misincorporation can arise from misread codons or mischarged tRNAs. Cells mitigate these errors through tRNA quality control, aminoacyl-tRNA synthetase fidelity, and general protein quality control mechanisms.

Causes of misincorporation include base mispairing due to tautomeric shifts, chemically damaged nucleotides, and imbalances in nucleotide pools or exposure to mutagens. Environmental factors and metabolic stress can elevate misincorporation frequencies.

Consequences vary: misincorporation in DNA can become a permanent mutation after replication, while errors in RNA or protein are typically transient and subject to degradation or refolding processes. Organisms rely on multiple repair and quality-control pathways to keep misincorporation rates low and minimize their impact.