Insights from xanthine and uracil DNA glycosylase activities of bacterial and human SMUG1: switching SMUG1 to UDG.

  title={Insights from xanthine and uracil DNA glycosylase activities of bacterial and human SMUG1: switching SMUG1 to UDG.},
  author={Rongjuan Mi and Liang Dong and Trupta Kaulgud and Kevin W Hackett and Brian N. Dominy and Weiguo Cao},
  journal={Journal of molecular biology},
  volume={385 3},
SMUG2 DNA glycosylase from Pedobacter heparinus as a new subfamily of the UDG superfamily.
New mechanistic insight is provided into the molecular mechanism of the UDG superfamily by identifying a family 3 SMUG1-like DNA glycoyslase from Pedobacter heparinus (named Phe SMUG2), which displays catalytic activities towards DNA containing uracil or hypoxanthine/xanthine.
Structural Basis of Substrate Specificity in Geobacter metallireducens SMUG1.
Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are critical to maintain genome integrity, in which the base excision repair pathway plays an
Specificity and Catalytic Mechanism in Family 5 Uracil DNA Glycosylase*
Mutational analysis coupled with molecular modeling and molecular dynamics analysis reveals that although hydrogen bonding to O2 of uracil underlies the UDG activity in a dissociative fashion, Tth UDGb relies on multiple catalytic residues to facilitate its excision of hypoxanthine and xanthine.
Sulfolobus acidocaldarius UDG Can Remove dU from the RNA Backbone: Insight into the Specific Recognition of Uracil Linked with Deoxyribose
Interestingly, they can remove U linked with deoxyribose from single-stranded RNA backbone, suggesting that the riboses on the backbone have less effect on the recognition of dU and hydrolysis of the C-N glycosidic bond.
Correlated Mutation in the Evolution of Catalysis in Uracil DNA Glycosylase Superfamily
Molecular dynamics simulations suggest that the correlated mutations in the doublet in motif 1 position the catalytic H155 in motif 2 to stabilize the leaving uracilate anion to study enzyme evolution and protein structure and function.
Identification of Escherichia coli Mismatch-specific Uracil DNA Glycosylase as a Robust Xanthine DNA Glycosylase*
Molecular modeling and molecular dynamics simulations reveal distinct hydrogen-bonding patterns in the active site of E. coli MUG that account for the specificity differences between MUG and human thymine DNA glycosylase as well as that between the wild type MUGand the Asn-140 and Ser-23 mutants.
An unconventional family 1 uracil DNA glycosylase in Nitratifractor salsuginis
This study underscores the diversity of paths that a uracil DNA glycosylase may take to acquire its unique structural and biochemical properties during evolution and reports a family 1 UNG homolog from Nitratifractor salsuginis with distinct biochemical features that differentiate it from conventionalfamily 1 UNGs.
A structural determinant in the uracil DNA glycosylase superfamily for the removal of uracil from adenine/uracil base pairs
The identification of an important structural determinant that underlies the functional difference between MUG and UNG is reported and the gain of function for A/U base pairs allows the MUG-K68N mutant to remove uracil incorporated into the genome during DNA replication.
Role of endonuclease III enzymes in uracil repair.


Mutational analysis of the damage-recognition and catalytic mechanism of human SMUG1 DNA glycosylase.
Single-strand selective monofunctional uracil-DNA glycosylase (SMUG1), previously thought to be a backup enzyme for uracil-DNA glycosylase, has recently been shown to excise 5-hydroxyuracil (hoU),
Mammalian 5-formyluracil-DNA glycosylase. 2. Role of SMUG1 uracil-DNA glycosylase in repair of 5-formyluracil and other oxidized and deaminated base lesions.
Data indicate a dual role of hSMUG1 as a backup enzyme for UNG and a primary repair enzyme for a subset of oxidized pyrimidines such as fU, hmU, and hoU.
Uracil–DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of base excision repair by distinct mechanisms
It is revealed that SMUG1 and UNG2 coordinate the initial steps of BER by distinct mechanisms, apparently adapted to rapid and highly coordinated repair of uracil (U:G and U:A) in replicating DNA, while the less efficient SMug1 may be more important in repair of deaminated cytosine (U-G) in non-replicating chromatin.
The versatile thymine DNA-glycosylase: a comparative characterization of the human, Drosophila and fission yeast orthologs.
This study characterized two newly discovered orthologs of TDG, the Drosophila melanogaster Thd1p and the Schizosaccharomyces pombe Thp1p proteins, and found that they have evolved with high structural flexibility to counter a broad range of DNA base damage in accordance with the specific needs of individual species.
Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil–DNA glycosylase
A model in which SMUG1 has evolved in higher eukaryotes as an anti‐mutator distinct from the UNG enzyme is proposed, the latter being largely localized to replication foci in mammalian cells to counteract de novo dUMP incorporation into DNA.
Structure and function in the uracil-DNA glycosylase superfamily.
  • L. Pearl
  • Biology, Chemistry
    Mutation research
  • 2000
A novel uracil‐DNA glycosylase with broad substrate specificity and an unusual active site
Pa‐UDGb is the first member of the UDG family that efficiently catalyses the removal of an aberrant purine, hypoxanthine, from DNA and is postulate that this enzyme has evolved to counteract the mutagenic threat of cytosine and adenine deamination, which becomes particularly acute in organisms living at elevated temperatures.