Self-promoted DNA interstrand cross-link formation by an abasic site.
The C4'-oxidized abasic site (C4-AP) is produced in DNA as a result of oxidative stress. A recent report suggests that this lesion forms interstrand cross-links. Using duplexes in which C4-AP is produced from a synthetic precursor, we show that the lesion produces interstrand cross-links in which both strands are in tact and cross-links in which the C4-AP containing strand is cleaved. The yields of these products are dependent upon the surrounding nucleotide sequence. When C4-AP is opposed by dA, cross-link formation occurs exclusively with an adjacent dA on the 5'-side. Moreover, formation of the lower molecular weight cross-link is promoted by an opposing adenine. When the opposing dA is replaced by dT, the activity of the adenine can be rescued by adding the free base. This is a rare example in which DNA promotes its own modification, an observation that is all the more important because of the biological significance of the product produced.
Sczepanski
Jonathan T
JT
Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Jacobs
Aaron C
AC
Greenberg
Marc M
MM
D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry; D020029:Base Pairing; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage; D010084:Oxidation-Reduction; D013936:Thymidine / Q000031:analogs & derivatives / Q000737:chemistry
D004247:DNA; D000225:Adenine; D013936:Thymidine