Interstrand DNA-DNA cross-link formation between adenine residues and abasic sites in duplex DNA.

Interstrand DNA-DNA cross-link formation between adenine residues and abasic sites in duplex DNA.
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DOI:
10.1021/ja410969x
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发表时间:
2014-03-05
影响因子:
15
通讯作者:
Gates KS
Gates KS
中科院分区:
化学1区
文献类型:
--
作者:
Price NE;Johnson KM;Wang J;Fekry MI;Wang Y;Gates KS

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DNA 结构中编码核碱基的丢失是产生脱碱基 (Ap) 位点的常见事件 (1)。 Ap位点作为环状半缩醛和开环醛的平衡混合物存在。醛是亲电官能团,可以与 DNA 中的亲核位点形成共价加合物。因此,Ap位点呈现出潜在反应性醛作为DNA内部结构的一部分。在这里,我们报道了双链 DNA 中 Ap 位点的醛基可以与相对链上腺嘌呤残基的 N6-氨基形成共价加合物的证据。由此产生的链间 DNA-DNA 交联发生在 5'-ApT/5'-AA 序列处,在生理相关条件下,产率非常高 (15-70%)。这种自然发生的 DNA 模板反应有可能在活细胞的遗传物质中产生交联。
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–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.
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