title: Interstrand DNA-DNA cross-link formation between adenine residues and abasic sites in duplex DNA.
abstract: The loss of a coding nucleobase from the structure of DNA is a common event that generates an abasic (Ap) site (1). Ap sites exist as an equilibrating mixture of a cyclic hemiacetal and a ring-opened aldehyde. Aldehydes are electrophilic functional groups that can form covalent adducts with nucleophilic sites in DNA. Thus, Ap sites present a potentially reactive aldehyde as part of the internal structure of DNA. Here we report evidence that the aldehyde group of Ap sites in duplex DNA can form a covalent adduct with the N(6)-amino group of adenine residues on the opposing strand. The resulting interstrand DNA-DNA cross-link occurs at 5'-ApT/5'-AA sequences in remarkably high yields (15-70%) under physiologically relevant conditions. This naturally occurring DNA-templated reaction has the potential to generate cross-links in the genetic material of living cells.
authors: Department of Chemistry and ‡Department of Biochemistry, University of Missouri , Columbia, Missouri 65211, United States.
authors: Nathan E
authors: NE
authors: Price
authors: Kevin M
authors: KM
authors: Johnson
authors: Jin
authors: J
authors: Wang
authors: Mostafa I
authors: MI
authors: Fekry
authors: Yinsheng
authors: Y
authors: Wang
authors: Kent S
authors: KS
authors: Gates
mesh_terms: D000225:Adenine / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: D000447:Aldehydes; D004247:DNA; D000225:Adenine