Stereoselective excision of thymine glycol from oxidatively damaged DNA
Autor: | Charles R. Iden, Elena I. Zaika, Maryann Wente, Arthur P. Grollman, Holly Miller, Andrea Fernandes, M. Cecilia Torres, Monica M. McTigue |
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Rok vydání: | 2004 |
Předmět: |
Saccharomyces cerevisiae Proteins
DNA Repair DNA repair DNA damage Oligonucleotides Biology DNA Glycosylases Substrate Specificity chemistry.chemical_compound Deoxyribonuclease (Pyrimidine Dimer) Genetics DNA-(Apurinic or Apyrimidinic Site) Lyase N-Glycosyl Hydrolases Oligonucleotide Escherichia coli Proteins Stereoisomerism DNA Articles DNA-(apurinic or apyrimidinic site) lyase Thymine Kinetics Oxidative Stress chemistry Biochemistry DNA glycosylase Oxidation-Reduction DNA Damage |
Zdroj: | Nucleic acids research. 32(1) |
ISSN: | 1362-4962 |
Popis: | DNA damage created by reactive oxygen species includes the prototypic oxidized pyrimidine, thymine glycol (Tg), which exists in oxidatively damaged DNA as two diastereoisomeric pairs. In Escherichia coli, Saccharomyces cerevesiae and mice, Tg is preferentially excised by endonuclease III (Endo III) and endonuclease VIII (Endo VIII), yNTG1 and yNTG2, and mNTH and mNEIL1, respectively. We have explored the ability of these DNA glycosylases to discriminate between Tg stereoisomers. Oligonucleotides containing a single, chromatographically pure (5S,6R) or (5R,6S) stereoisomer of Tg were prepared by oxidation with osmium tetroxide. Steady-state kinetic analyses of the excision process revealed that Endo III, Endo VIII, yNTG1, mNTH and mNEIL1, but not yNTG2, excise Tg isomers from DNA in a stereoselective manner, as reflected in the parameter of catalytic efficiency (kcat/Km). When DNA glycosylases occur as complementary pairs, failure of one or both enzymes to excise their cognate Tg stereoisomer from oxidatively damaged DNA could have deleterious consequences for the cell. |
Databáze: | OpenAIRE |
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