DNA glycosylase

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Contents

Function

DNA glycosylase (DG) are enzymes which remove damaged DNA bases by flipping them out of the double helix followed by their cleavage. Monofunctional DG have only glycosylase activity; bifunctional DG also act as lysates; ADG, UDG, TDG remove adenine, uracil, thymine from DNA.[1]

  • Adenine DNA glycosylase is also called MutY. MutY has a role in prevention of DNA mutations resulting from oxidative damage forming the mutated base oxoG. DNA polymerase misreads oxoG and pairs it with adenine instead of cytosine. MutY removes adenine from the mismatched oxoG:A pair. MutY contains a 4Fe4S cluster.
  • Uracil DNA glycosylase (UDG) eliminates uracil from DNA and thus preventing mutagenesis. UDG initiates the base excision repair pathway. UDG excises uracil in both AU and GU pairs. UDG can repair 10,000 damaged bases in the human cell per day[2]. See also DNA Repair.
  • Thymine DNA glycosylase removes thymine moieties from mismatched G/T, C/T and T/T.
  • Smug1 is a single-strand selective monofunctional UDG.
  • 8-oxoguanine DNA glycosylase recognize oxidized bases.
  • Human 8-oxoguanine GD is named hOgg1. See details on Ogg1 in 8-Oxoguanine Glycosylase.
  • Methyladenine DNA glycosylase recognize methylated adenine; for details see Alka1.
  • Formamidopyrimidine DG (FPG) or MutM or Fapy-DNA glycosylase removes oxidized purines from damaged DNA. More about FPG in
  • Fpg Nei Protein Family
  • Fpg Nei Protein Superfamily.

Structural highlights

MutY uses base flipping to twist the mispaired adenine out of the DNA helix and into the MutY active site. MutY contains 2 domains: C-terminal domain and catalytic domain containing a helix-hairpin-helix.

  • Adenine DNA glycosylase containing Fe4S4 cluster with DNA containing an mispaired adenine 8OG and Ca+2.
  • Mispaired adenine 8OG binding site.
  • Fe4S4 cluster binds to 3 Cys residues.
  • Ca+2 ion coordination site (PDB code 1rrs)[3]. Water molecules shown as red spheres.

3D Structures of DNA glycosylase

DNA glycosylase 3D structures


Structure of adenine DNA glycosylase containing Fe4S4 cluster complex with DNA containing an oxoG base, deoxy-ribofuranose phosphate and Ca+2 ion (green) (PDB code 1rrs).

Drag the structure with the mouse to rotate

References

  1. ↑ Fromme JC, Banerjee A, Verdine GL. DNA glycosylase recognition and catalysis. Curr Opin Struct Biol. 2004 Feb;14(1):43-9. PMID:15102448 doi:http://dx.doi.org/10.1016/j.sbi.2004.01.003
  2. ↑ Willetts KE, Rey F, Agostini I, Navarro JM, Baudat Y, Vigne R, Sire J. DNA repair enzyme uracil DNA glycosylase is specifically incorporated into human immunodeficiency virus type 1 viral particles through a Vpr-independent mechanism. J Virol. 1999 Feb;73(2):1682-8. PMID:9882380
  3. ↑ Fromme JC, Banerjee A, Huang SJ, Verdine GL. Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase. Nature. 2004 Feb 12;427(6975):652-6. PMID:14961129 doi:10.1038/nature02306

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