Structure and function in the uracil-DNA glycosylase superfamily

Mutat Res. 2000 Aug 30;460(3-4):165-81. doi: 10.1016/s0921-8777(00)00025-2.


Deamination of cytosine to uracil is one of the major pro-mutagenic events in DNA, causing G:C-->A:T transition mutations if not repaired before replication. Repair of uracil-DNA is achieved in a base-excision pathway initiated by a uracil-DNA glycosylase (UDG) enzyme of which four families have so far been identified. Family-1 enzymes are active against uracil in ssDNA and dsDNA, and recognise uracil explicitly in an extrahelical conformation via a combination of protein and bound-water interactions. Extrahelical recognition requires an efficient process of substrate location by 'base-sampling' probably by hopping or gliding along the DNA. Family-2 enzymes are mismatch specific and explicitly recognise the widowed guanine on the complementary strand rather than the extrahelical scissile pyrimidine. This allows a broader specificity so that some Family-2 enzymes can excise uracil and 3, N(4)-ethenocytosine from mismatches with guanine. Although structures are not yet available for Family-3 (SMUG) and Family-4 enzymes, sequence analysis suggests similar overall folds, and identifies common active site motifs but with a surprising lack of conservation of catalytic residues between members of the super-family.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / chemistry
  • Bacterial Proteins / chemistry
  • Base Pairing
  • Cytosine / analogs & derivatives
  • Cytosine / metabolism
  • DNA / chemistry
  • DNA / metabolism
  • DNA Damage
  • DNA Glycosylases*
  • DNA Repair*
  • Deamination
  • Escherichia coli / enzymology
  • Escherichia coli Proteins*
  • Herpesvirus 1, Human / enzymology
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family
  • N-Glycosyl Hydrolases / chemistry*
  • N-Glycosyl Hydrolases / classification
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / physiology
  • Point Mutation
  • Protein Binding
  • Protein Conformation
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thermotoga maritima / enzymology
  • Thymine DNA Glycosylase*
  • Uracil / chemistry
  • Uracil-DNA Glycosidase
  • Viral Proteins / chemistry


  • 3,N(4)-ethenocytosine
  • Archaeal Proteins
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Viral Proteins
  • Uracil
  • Cytosine
  • DNA
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Thymine DNA Glycosylase
  • Uracil-DNA Glycosidase
  • double-strand uracil-DNA glycosylase, E coli
  • mismatch-specific thymine uracil-DNA glycosylase