Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA.
Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA.
复制标题
DOI：
10.1021/acs.chemrestox.1c00004
复制
发表时间：
2021-04-19
影响因子：
4.1
通讯作者：
Gates KS
中科院分区：
文献类型：
--
作者：
Varela JG;Pierce LE;Guo X;Price NE;Johnson KM;Yang Z;Wang Y;Gates KS
双链DNA中链间交联的形成在生物学、医学和生物技术中是重要的。由脱碱基（脱嘌呤或AP）位点的醛残基与双链体DNA的相对链上的鸟嘌呤或腺嘌呤残基的环外氨基的反应产生的链间交联先前已被表征。典型的核碱基胞嘧啶具有环外氨基，但其通过与AP位点反应形成链间交联的能力在此之前尚未被表征。这里显示，在具有位于相对链上AP位点的3 '侧的一个核苷酸的错配胞嘧啶残基的序列中产生了大量的链间交联（例如5' XA/5 'CA，其中X=AP）。dC-AP交联的形成是pH依赖性的，在pH 5下的产率显著高于pH 7。一旦形成，dC-AP交联是相当稳定的，在pH 7和37 °C下96小时内显示出小于5%的解离。当胞嘧啶残基与其Watson-Crick伴侣鸟嘌呤配对时，没有观察到显著的交联产率。还表明，单个AP位点可以与某些序列中的多个核碱基交联配偶体接合。具体地，dG-AP和dC-AP交联在序列5 'CXC/5' GAA（X=AP）中以动态平衡共存。在该序列中，dC-AP交联占主导地位。然而，在NaBH 3CN的存在下，混合物中存在的少量dG-AP交联的不可逆还原使平衡远离dC-AP交联向dG-AP red交联的良好产率移动。
The formation of interstrand cross-links in duplex DNA is important in biology, medicine, and biotechnology. Interstrand cross-links arising from the reaction of the aldehyde residue of an abasic (apurinic or AP) site with the exocyclic amino groups of guanine or adenine residues on the opposing strand of duplex DNA have previously been characterized. The canonical nucleobase cytosine has an exocyclic amino group but its ability to form interstrand cross-links by reaction with an AP site has not been characterized before now. Here it is shown that substantial yields of interstrand cross-links are generated in sequences having a mispaired cytosine residue located one nucleotide to the 3’-side of the AP site on the opposing strand (e.g. 5’XA/5’CA, where X=AP). Formation of the dC-AP cross-link is pH-dependent, with significantly higher yields at pH 5 than pH 7. Once formed, the dC-AP cross-link is quite stable, showing less than 5% dissociation over the course of 96 h at pH 7 and 37 °C. No significant yields of cross-link are observed when the cytosine residue is paired with its Watson-Crick partner guanine. It was also shown that a single AP site can engage with multiple nucleobase cross-linking partners in some sequences. Specifically, the dG-AP and dC-AP cross-links coexist in dynamic equilibrium in the sequence 5’CXC/5’GAA (X=AP). In this sequence, the dC-AP cross-link dominates. However, in the presence of NaBH3CN, irreversible reduction of small amounts of the dG-AP cross-link present in the mixture shifts the equilibria away from the dC-AP cross-link toward good yields of the dG-APred cross-link.
登录
查看更多内容
影响因子：
2.9
作者：
Kurtz, AJ;Dodson, ML;Lloyd, RS
通讯作者：
Lloyd, RS
影响因子：
2.1
作者：
HOPKINS, PB;MILLARD, JT;RAUCHER, S
通讯作者：
RAUCHER, S
影响因子：
15
作者：
Catalano MJ;Liu S;Andersen N;Yang Z;Johnson KM;Price NE;Wang Y;Gates KS
通讯作者：
Gates KS
影响因子：
3.6
作者：
AbdelMagid, AF;Carson, KG;Shah, RD
通讯作者：
Shah, RD
影响因子：
4.1
作者：
Gates, Kent S.
通讯作者：
Gates, Kent S.