Enzymology of the repair of etheno adducts in mammalian cells and in Escherichia coli.
Exocyclic adducts are generated in cellular DNA by reaction with epoxides that are formed metabolically from various industrial pollutants and by reaction with activated aldehydes that arise during membrane lipid peroxidation. The etheno (epsilon) derivatives of purine and pyrimidine bases, e.g. 3,N4-ethenocytosine, 1,N6-ethenoadenine, N2,3-ethenoguanine and 1,N2-ethenoguanine, are probably involved in carcinogenesis because they are highly mutagenic and genotoxic. Therefore, the repair processes that eliminate exocyclic adducts from DNA should play a crucial role in maintaining the stability of the genetic information. The DNA glycosylases implicated in the repair of etheno adducts have been identified. Human and Escherichia coli 3-methyladenine-DNA-glycosylases excise 1,N6-ethenoadenine residues. We have identified two homologous proteins present in human cells and E. coli that remove 3,N4-ethenocytosine residues by DNA glycosylase activity. The human enzyme is an activity of the mismatch-specific thymine-DNA glycosylase, while the bacterial enzyme is an activity of the double-stranded uracil-DNA glycosylase, i.e., the homologue of the human enzyme. The fact that 1,N6-ethenoadenine and 3,N4-ethenocytosine are recognized and efficiently excised by DNA glycosylases in vitro suggests that these enzymes may be responsible for the repair of these mutagenic lesions in vivo and may contribute importantly to genetic stability.
Saparbaev
M
M
Groupe Reparation des lésions Radio- et Chimio-induites, UMR 1772 CNRS Institut Gustave Roussy, Villejuif, France.
Laval
J
J
D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003562:Cytidine / Q000031:analogs & derivatives* / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D045647:DNA Glycosylases; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009690:Nucleic Acid Conformation; D051981:Uracil-DNA Glycosidase
C012962:3,N(4)-ethenocytidine; C018289:3,N(4)-ethenocytosine; D001426:Bacterial Proteins; D018736:DNA Adducts; D005656:Fungal Proteins; C004981:1,N(6)-ethenoadenine; D003562:Cytidine; D003596:Cytosine; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; C076131:DNA-3-methyladenine glycosidase II; D000225:Adenine