Eukaryotic Mismatch Repair in Relation to DNA Replication

Annu Rev Genet. 2015;49:291-313. doi: 10.1146/annurev-genet-112414-054722.

Abstract

Three processes act in series to accurately replicate the eukaryotic nuclear genome. The major replicative DNA polymerases strongly prevent mismatch formation, occasional mismatches that do form are proofread during replication, and rare mismatches that escape proofreading are corrected by mismatch repair (MMR). This review focuses on MMR in light of increasing knowledge about nuclear DNA replication enzymology and the rate and specificity with which mismatches are generated during leading- and lagging-strand replication. We consider differences in MMR efficiency in relation to mismatch recognition, signaling to direct MMR to the nascent strand, mismatch removal, and the timing of MMR. These studies are refining our understanding of relationships between generating and repairing replication errors to achieve accurate replication of both DNA strands of the nuclear genome.

Keywords: DNA mismatch repair; genome instability; mutation rate; mutator; replication fidelity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • DNA / genetics
  • DNA Damage
  • DNA Mismatch Repair / physiology*
  • DNA Replication / physiology*
  • Escherichia coli / genetics
  • Genomic Instability
  • Humans
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • DNA