Interstrand DNA鈥揇NA Cross-Link Formation Between Adenine Residues and Abasic Sites in Duplex DNA

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• 作者：Nathan E. Price ; Kevin M. Johnson ; Jin Wang ; Mostafa I. Fekry ; Yinsheng Wang ; Kent S. Gates
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：March 5, 2014
• 年：2014
• 卷：136
• 期：9
• 页码：3483-3490
• 全文大小：449K
• 年卷期：v.136,no.9(March 5, 2014)
• ISSN：1520-5126

文摘

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 N⁶-amino group of adenine residues on the opposing strand. The resulting interstrand DNA鈥揇NA cross-link occurs at 5鈥?ApT/5鈥?AA sequences in remarkably high yields (15鈥?0%) under physiologically relevant conditions. This naturally occurring DNA-templated reaction has the potential to generate cross-links in the genetic material of living cells.