Abstract
Reactive oxygen species from endogenous and exogenous sources induce varieties of oxidative damage to DNA. The response of DNA glycosylases and DNA polymerases to such damage is best studied by using defined oligonucleotide substrates containing unique lesions. Recently, chemical synthesis of oligonucleotides containing the stereoisomers of thymine glycol and the formamidopyrimidine derivatives of guanine and adenine has been established. NEIL1, NEIL2, and SMUG1 are the new members of mammalian DNA glycosylases involved in the repair of oxidative DNA damage. Their repair function has been assessed by the analyses of damage specificity of purified proteins and cellular activity. The lack of overt phenotypes of mice deficient in DNA glycosylases for oxidative damage (NTH1, OGG1, and MYH) suggest more elaborate repair networks and functional redundancy of participating DNA glycosylases in mammals than in prokaryotes.
