Reactivity of the C2‘-Oxidized Abasic Lesion and Its Relevance to Interactions with Type I Base Excision Repair Enzymes
| Autor: | Jaeseung Kim, Summer E. Young, Marc M. Greenberg, Cortney R. Kreller |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pyrrolidines
DNA Repair Nitrogen Lysine Oligonucleotides Borohydrides Toxicology Cleavage (embryo) Lesion chemistry.chemical_compound medicine Schiff Bases biology Oligonucleotide Hydrolysis Active site General Medicine Base excision repair Endonucleases Oxidative Stress Biochemistry chemistry DNA glycosylase biology.protein Indicators and Reagents medicine.symptom Peptides DNA DNA Damage |
| Zdroj: | Chemical Research in Toxicology. 19:463-468 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx060001q |
| Popis: | The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. C2-AP is incised by phosphodiesterases, but is not a substrate for endonuclease III even though a Schiff base is formed (Greenberg, M. M., et al. (2004) Biochemistry 43, 15217). A chemically synthesized oligonucleotide was used to study C2-AP reactivity under alkaline conditions and with nitrogen nucleophiles chosen to mimic the lysine or N-terminal proline side chains present in the active site of Type I base excision repair enzymes. Alkaline cleavage of the C2-AP lesion produces 3'-phosphoglycoaldehyde and 3'-phosphate termini. The former is degraded further to 3'-hydroxyl groups. Cleavage at the C2-AP lesion is enhanced by small peptides, which form Schiff base intermediates with the lesion. C2-AP cleavage by Lys.Trp.Lys and Lys.Trp.Gly.Lys suggests that the inability of endonuclease III to cleave the lesion is due to the absence of appropriately positioned functional groups to take advantage of formation of the covalent intermediate. These observations leave open the possibility that the C2-AP lesion may be a substrate for other Type I repair enzymes. |
| Databáze: | OpenAIRE |
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