mispairing

Mispairing is the incorrect pairing of nucleotides in nucleic acids or the incorrect interaction of molecular components during gene expression, leading to a mismatch. In DNA replication, mispairing occurs when a DNA polymerase inserts a noncomplementary base opposite the template, creating a mismatched base pair such as G–T or A–C. Mispairs arise from tautomeric shifts, chemical modifications, or errors in polymerase fidelity, and they are a key source of spontaneous mutations.

Consequence and repair: If a mispair is not corrected before or during replication, it can be propagated as a permanent mutation after a second round of replication. Cells use proofreading by the polymerase’s 3′→5′ exonuclease activity and post-replicative mismatch repair to correct most mispairs. In bacteria, mismatch repair involves MutS, MutL, and MutH; in eukaryotes, the MutSα complex (MSH2–MSH6) and MutLα (MLH1–PMS2) perform similar roles. Strand discrimination often relies on nicks on the newly synthesized strand or, in bacteria, DNA methylation patterns.

In translation, mispairing can occur when a tRNA anticodon pairs with a noncomplementary codon, causing amino acid misincorporation. The ribosome and tRNA selection mechanisms minimize errors, but some level of translational mispairing is tolerated and can influence protein diversity and quality.

In RNA, mispairing may refer to noncanonical base pairs in RNA structure that affect folding and function. Across contexts, mispairing represents a fundamental source of genetic variation and is countered by cellular quality-control systems.