MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis

Nature. 1992 Jan 16;355(6357):273-5. doi: 10.1038/355273a0.


Errors in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. This error-avoiding process is catalysed by a protein encoded by the mutT gene of Escherichia coli, mutations of which increase the occurrence of A.T----C.G transversions 100 to 10,000 times the level of the wild type. Spontaneous oxidation of dGTP forms 8-oxo-7,8-dihydro-2'-dGTP (8-oxodGTP), which is inserted opposite dA and dC residues of template DNA with almost equal efficiency, and the MutT protein specifically degrades 8-oxodGTP to the monophosphate. This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Composition
  • Base Sequence
  • DNA Replication*
  • Deoxyadenine Nucleotides / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins*
  • Hydrolysis
  • Kinetics
  • Molecular Sequence Data
  • Mutation*
  • Phosphoric Monoester Hydrolases / metabolism*
  • Pyrophosphatases
  • Substrate Specificity
  • Templates, Genetic


  • Bacterial Proteins
  • Deoxyadenine Nucleotides
  • Escherichia coli Proteins
  • Phosphoric Monoester Hydrolases
  • Pyrophosphatases
  • mutT protein, E coli
  • 2'-deoxyadenosine triphosphate