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The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2018-10-26 , DOI: 10.1016/j.omtn.2018.10.014
Boleslaw T. Karwowski

The interaction of chemical and physical agents with genetic material can lead to almost 80 different DNA damage formations. The targeted intentional DNA damage by radiotherapy or chemotherapy is a front-line anticancer therapy. An interstrand cross-link can result from ionization radiation or specific chemical agents, such as trans-/cisplatin activity. Here, the influence of the adenine and thymidine (AT) interstrand linkage, the covalent bond between the adenine N6 and thymidine C5 methylene group, on the isolated base pair as well as double-stranded DNA (dsDNA) was taken into quantum mechanical/molecular mechanical (QM/MM) consideration at the m062x/6-31+G*:UFF level of theory in the aqueous phase. All the results presented in this article, for the first time, show that an AT-interstrand cross-link (ICL) changes the positive and negative charge migration process due to a higher activation energy forced by the cross-link’s presence. However, the final radical cation destination in cross-linked DNA is left in the same place as in a native double-stranded-deoxyoligonucleotide. Additionally, the direction of the radical anion transfer was found to be opposite to that of native dsDNA. Therefore, it can be postulated that the appearance of the AT-ICL does not disturb the hole migration in the double helix, with subsequent effective changes in the electron migration process.



中文翻译:

AT Interstrand交叉链接:结构,电子性能,以及对dsDNA中电荷转移的影响。

化学和物理因素与遗传物质的相互作用可导致近80种不同的DNA损伤形成。通过放射疗法或化学疗法有针对性的故意破坏DNA是一线抗癌疗法。链间交联可以由电离辐射或特定的化学试剂(例如反式/顺铂活性)引起。在这里,将腺嘌呤和胸苷(AT)链间连接,腺嘌呤N6和胸苷C5亚甲基之间的共价键对分离的碱基对以及双链DNA(dsDNA)的影响纳入量子力学/分子在m062x / 6-31 + G *:UFF的水相理论水平下进行机械(QM / MM)考虑。本文中首次提出的所有结果,结果表明,AT-链间交联键(ICL)改变了正电荷迁移和负电荷迁移过程,这是由于交联的存在迫使其具有更高的活化能。但是,交联DNA中最终的自由基阳离子目的地与天然双链保留在同一位置-脱氧寡核苷酸。另外,发现自由基阴离子转移的方向与天然dsDNA的方向相反。因此,可以假定,AT-ICL的出现不会干扰双螺旋中的空穴迁移,从而在电子迁移过程中具有随后的有效变化。

更新日期:2018-10-26
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