Direct formation of the C5'-radical in the sugar-phosphate backbone of DNA by high-energy radiation.
Direct formation of the C5'-radical in the sugar-phosphate backbone of DNA by high-energy radiation.
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DOI：
10.1021/jp3023919
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发表时间：
2012-05-24
影响因子：
3.3
通讯作者：
Sevilla, Michael D.
中科院分区：
文献类型：
--
作者：
Adhikary, Amitava;Becker, David;Palmer, Brian J.;Heizer, Alicia N.;Sevilla, Michael D.
在DNA糖-磷酸主链中形成的中性糖自由基被认为是DNA链断裂和交联等重要生物学损伤的前体。在这项工作中，我们提出了电子自旋共振（ESR）证据，表明C5 ‘ （C5 ’•）上的糖自由基是γ和Ar离子束辐照水合DNA样品形成的最丰富的糖自由基之一（约30%）。以磷酸二甲酯为糖-磷酸骨架模型，进行了γ辐照磷酸二甲酯的ESR和DFT理论研究。CH3OP(O2−)OCH2•由直接电离的磷酸二甲酯甲基在77 K下脱质子生成。CH3OP(O2−)OCH2•的形成与二甲基磷酸浓度（纯溶液或水溶液）或ph值无关。DNA中发现的C5′•和CH3OP(O2−)OCH2•的ESR光谱没有显示出可观察到的β-磷超精细偶联（HFC）。此外，在DNA中发现的C5 ‘•没有显示出显著的C4 ’ -H β -质子HFC。应用DFT/B3LYP/6-31G(d)方法，对CH3OP(O2−)OCH2•中含磷HFC的构象依赖性进行了研究，结果表明，在CH3OP(O2−)OCH2•的最小能量构象中，CH3OP(O2−)OCH2•具有可忽略的β-磷HFC。基于这些结果，辐射诱导的C5 '•的形成是通过直接电离的糖-磷酸主链的快速去质子化而发生的，并且这种去质子化的速度必须快于从电离的糖-磷酸主链到DNA碱基的未配对自旋（空穴）的能量下移的速度。此外，在辐照DNA中发现C5 '•的构象不表现出β质子或β磷hfc。
Neutral sugar radicals formed in DNA sugar-phosphate backbone are well-established as precursors of biologically important damage such as DNA-strand scission and crosslinking. In this work, we present electron spin resonance (ESR) evidence showing that the sugar radical at C5′ (C5′•) is one of the most abundant (ca. 30%) sugar radicals formed by γ- and Ar ion-beam irradiated hydrated DNA samples. Taking dimethyl phosphate as a model of sugar-phosphate backbone, ESR and theoretical (DFT) studies of γ-irradiated dimethyl phosphate were carried out. CH3OP(O2−)OCH2• is formed via deprotonation from the methyl group of directly ionized dimethyl phosphate at 77 K. Formation of CH3OP(O2−)OCH2• is independent of dimethyl phosphate concentration (neat or in aqueous solution) or pH. ESR spectra of C5′• found in DNA and of CH3OP(O2−)OCH2• do not show an observable β-phosphorous hyperfine coupling (HFC). Further, C5′• found in DNA does not show a significant C4′-H β–proton HFC. Applying the DFT/B3LYP/6-31G(d) method, a study of conformational dependence of the phosphorous HFC in CH3OP(O2−)OCH2• shows that in its minimum energy conformation, CH3OP(O2−)OCH2• has a negligible β-phosphorous HFC. Based on these results, formation of radiation-induced C5′• is proposed to occur via a very rapid deprotonation from the directly ionized sugar-phosphate backbone and rate of this deprotonation must be faster than that of energetically downhill transfer of the unpaired spin (hole) from ionized sugar-phosphate backbone to the DNA bases. Moreover, C5′• in irradiated DNA is found to be in a conformation that does not exhibit β proton or β phosphorous HFCs.
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影响因子：
4.4
作者：
ALEXANDER, C;FRANKLIN, CE
通讯作者：
FRANKLIN, CE
影响因子：
15
作者：
Adhikary A;Kumar A;Khanduri D;Sevilla MD
通讯作者：
Sevilla MD
影响因子：
15
作者：
Adhikary A;Khanduri D;Sevilla MD
通讯作者：
Sevilla MD
影响因子：
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作者：
Close, David M.
通讯作者：
Close, David M.
影响因子：
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作者：
Close, DM
通讯作者：
Close, DM