UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB

Mol Cell. 2007 Dec 28;28(6):1058-70. doi: 10.1016/j.molcel.2007.10.025.

Abstract

DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / genetics
  • Blotting, Far-Western
  • DNA Polymerase beta / chemistry
  • DNA Polymerase beta / genetics
  • DNA Polymerase beta / metabolism*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • Rec A Recombinases / chemistry
  • Rec A Recombinases / genetics
  • Rec A Recombinases / metabolism*
  • Sequence Homology, Amino Acid

Substances

  • DinB protein, E coli
  • Escherichia coli Proteins
  • DNA Polymerase beta
  • Rec A Recombinases
  • DNA-Directed DNA Polymerase
  • UmuD protein, E coli