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DNA Charge Transport Chemistry & Biology

DNA电荷传输化学

基本信息

批准号：
8197925
负责人：
JACQUELINE K BARTON
金额：
$ 36.63万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-03-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8197925
关键词：
Archaea Base Excision Repairs Biological Biological Assay Biology Cancerous Cells Charge Chemistry Complex Coupled DNA DNA Binding DNA Damage DNA Repair DNA-Binding Proteins Detection Distant Electrochemistry Electron Transport Electrons Enzymes Escherichia coli Goals Guanine Hela Cells Homologous Gene Human In Vitro Injection of therapeutic agent Lesion Ligands Malignant Neoplasms Mediating Mitochondria Mitochondrial DNA Mutation Oxidants Oxidative Stress Predisposition Process Proteins Rhodium Role Series Signal Transduction Site Spectrum Analysis Testing Transcription Coactivator Transcription Initiation Transcriptional Regulation absorption abstracting analog base cyclopropylamine endonuclease III genetic regulatory protein mitochondrial DNA mutation mutant oxidation oxidative DNA damage oxidative damage repair enzyme repaired research study

项目摘要

Project Summary/Abstract This proposal aims to characterize the chemistry and biology associated with DNA-mediated charge transport (CT). Specifically, roles for DNA CT in how DNA is damaged and repaired under oxidative stress will be explored. Experiments are proposed to examine oxidative DNA damage at long range as well as DNA-mediated signaling to regulatory proteins. We will examine the distance range over which oxidative damage is funneled to a control sequence in mitochondria using rhodium photooxidants to generate damage at distant sites. Mitochondrial DNA mutations and their correlations with cancers will also be determined. We will further delineate the role of DNA CT in DNA damage detection by base excision repair (BER) enzymes that contain 4Fe-4S clusters. We will prepare a series of BER enzyme mutants to characterize the path for DNA/protein CT. CT will be probed using DNA electrochemistry, EPR, transient absorption spectroscopy and AFM. In vitro protein oxidations by guanine radicals in DNA will be generated by hole injection from tethered metallointercalators. Biological assays of repair in E. coli will test how effectively mutants of two BER enzymes, MutY and Endonuclease III (EndoIII), cooperate in detecting base lesions. Correlations will be drawn between this biological helper function, DNA/protein CT studies, and cancer predispositions in human MutY homologues. DNA-mediated CT for transcriptional regulation will also be examined in soxR, a transcriptional activator from E. coli containing an Fe-S cluster. We will test the initiation of transcription from a distance through long range oxidation of DNA-bound soxR using tethered photooxidants. Paralleling these CT studies with DNA-bound proteins, we will construct DNA assemblies containing tethered metallointercalators, cyclometallated complexes of Ir and Re(CO) diimine complexes, to characterize DNA-mediated reduction chemistry versus long range DNA- mediated oxidations.

项目总结/摘要该提案旨在表征与DNA介导的电荷传输（CT）。具体来说，DNA CT在DNA如何在将探讨氧化应激。实验提出检查氧化DNA损伤在长时间范围以及DNA介导的信号传导到调节蛋白。我们将检查距离范围氧化损伤在线粒体中被引导到一个控制序列光氧化剂在远处产生损伤。线粒体DNA突变及其与还将确定与癌症的相关性。我们将进一步阐明DNA CT在DNA中的作用通过含有4Fe-4S簇的碱基切除修复（BER）酶进行损伤检测。我们将准备一系列BER酶突变体来表征DNA/蛋白质CT的路径。CT将使用 DNA电化学、电子顺磁共振、瞬态吸收光谱和原子力显微镜。体外蛋白质氧化 DNA中的鸟嘌呤自由基将通过束缚的金属嵌入剂的空穴注入产生。 E.大肠杆菌将测试两种BER酶MutY和核酸内切酶III（EndoIII），配合检测碱基病变。相关性将被绘制在这种生物辅助功能，DNA/蛋白质CT研究，以及人类MutY中的癌症易感性同源物DNA介导的转录调控CT也将在soxR中进行检查，转录激活因子E. coli中含有Fe-S簇。我们将测试通过DNA结合的soxR的远程氧化从远处转录，光氧化剂除了这些CT研究与DNA结合的蛋白质，我们将构建DNA 含有栓系金属插层剂的组装体，Ir和Re（CO）的环化络合物二亚胺复合物，以表征DNA介导的还原化学与长距离DNA- 介导的氧化。

项目成果

期刊论文数量（63）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Using metal complex reduced states to monitor the oxidation of DNA.

DOI：
10.1021/ic201511y
发表时间：
2011-12-05
期刊：
Inorganic chemistry
影响因子：
4.6
作者：
Olmon ED;Hill MG;Barton JK
通讯作者：
Barton JK

Mechanisms for DNA charge transport.

DOI：
10.1021/cr900228f
发表时间：
2010-03-10
期刊：
Chemical reviews
影响因子：
62.1
作者：
Genereux JC;Barton JK
通讯作者：
Barton JK

Electron transfer between metal complexes bound to DNA: is DNA a wire?

与 DNA 结合的金属复合物之间的电子转移：DNA 是一根电线吗？

DOI：
发表时间：
1996
期刊：
Metal ions in biological systems.
影响因子：
0
作者：
Stemp,ED;Barton,JK
通讯作者：
Barton,JK

Charge photoinjection in intercalated and covalently bound [Re(CO)3(dppz)(py)]+-DNA constructs monitored by time-resolved visible and infrared spectroscopy.

在插入和共价结合[RE（CO）3（DPPZ）（PY）]+DNA构建体中，通过时间分辨可见和红外光谱监测的DNA构建体。

DOI：
10.1021/ja205568r
发表时间：
2011-08-31
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Olmon, Eric D.;Sontz, Pamela A.;Blanco-Rodriguez, Ana Maria;Towrie, Michael;Clark, Ian P.;Vlcek, Antonin, Jr.;Barton, Jacqueline K.
通讯作者：
Barton, Jacqueline K.

Rapid radical formation by DNA charge transport through sequences lacking intervening guanines.

DNA 电荷传输通过缺乏插入鸟嘌呤的序列而快速形成自由基。