Protein Name

human 8-oxoguanine glycosylase (hOGG1) bound to DNA


Homo sapiens (human)

Biological Context

The maintenance of genetic stability, i.e. minimum variation in the DNA sequence, is essential for the correct functioning of cells and hence organisms. DNA is extremely susceptible to spontaneous changes due to exposure to various external stimuli such as heat, radiation, and other DNA damaging substances. These random changes in the DNA sequence need to be corrected or repaired efficiently. Accumulation of such changes or mutations results in their propagation during DNA replication, and in the production of dysfunctional or mutant proteins that are harmful to the cell. Indeed, the inability of cells to repair damaged DNA causes various diseases in humans such as cancer, neurological abnormalities and congenital abnormalities, among others. DNA damage can occur in various forms such as spontaneous changes in single bases, single strand breaks or double strand breaks. Each form of DNA damage is processed and repaired by different sets of enzymes that specifically recognize it. One of the causes of mutations in DNA is the attack of reactive oxygen species on bases. Reactive oxygen species are electrophilic oxidants that can either escape from the mitochondria or be generated as a result of exposure to ionizing radiation or certain chemicals. Oxidation of guanine bases by such partially reduced oxygen species results in the formation of 7,8-dihydro-8-oxoguanine (oxoG). OxoG preferentially pairs with adenine (A) instead of the normal cytosine (C), resulting in a transversion mutation from a G.C pair to a T.A pair after DNA replication. Human 8-oxoguanine DNA glycosylase (hOGG1) is an enzyme that specifically recognizes oxoG.C base pairs and repairs them by removing the oxoG base and cleaving the DNA.

Structure Description


The structure shown here is that of the catalytic core of hOGG1 bound to DNA at the oxoG.C base pair. The enzyme is a member of a superfamily of base-excision DNA repair enzymes and contains the characteristic helix-hairpin- helix motif. The oxoG residue is extruded from the helix and inserted into the extrahelical active-site pocket of hOGG1. The complementary C is still inside the DNA helix and makes specific contacts with side chains of certain residues in the enzyme causing a kink in the DNA. The active site specifically recognizes oxidized guanines and excludes other normal DNA bases. Loss of proper function of the OGG1 enzyme in mice is known to cause premature aging, increased levels of genomic oxoG and accelerated basal mutation rates.

Protein Data Bank (PDB)



Bruner, S.D. Norman, D.P. Verdine, G.L.; "Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA."; Nature; (2000) 403:859-866 PubMed:10706276.


author: Ashwini Patil

Japanese version:PDB:1EBM