Self-promoted DNA interstrand cross-link formation by an abasic site. Academic Article uri icon

abstract

  • 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.

author list (cited authors)

  • Sczepanski, J. T., Jacobs, A. C., & Greenberg, M. M

citation count

  • 65

complete list of authors

  • Sczepanski, Jonathan T||Jacobs, Aaron C||Greenberg, Marc M

publication date

  • January 2008