| Abstract
| - 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 Schiffbase is formed (Greenberg, M. M., et al. (2004) Biochemistry43, 15217). A chemically synthesizedoligonucleotide was used to study C2-AP reactivity under alkaline conditions and with nitrogennucleophiles chosen to mimic the lysine or N-terminal proline side chains present in the active site ofType 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 atthe 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 tocleave the lesion is due to the absence of appropriately positioned functional groups to take advantageof formation of the covalent intermediate. These observations leave open the possibility that the C2-APlesion may be a substrate for other Type I repair enzymes.
|
