COOPERATIVE INTERACTIONS IN DNA REPAIR
DNA 修复中的合作相互作用
基本信息
- 批准号:6760656
- 负责人:
- 金额:$ 5.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-04-01 至 2004-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Our goal is to elucidate mechanisms by which DNA-repair proteins perform their essential biological functions. As immediate objectives, we will investigate the interactions of human 0 6- alkylguanine-DNA alkyltransferase (AGT) with O6-alkylguanine (lesion)-containing and lesion-free DNAs. AGT repairs pro-mutagenic O -alkylguanine residues in DNA. It binds DNA with substantial cooperativity but little sequence or base composition dependence. These results argue against mechanisms of target recognition that depend strongly on sequence. An alternate possibility, which comprises the central hypothesis of this application, is that cooperative DNA binding and access to DNA modulate the binding distributions of AGT and its rate of DNA-repair. To test this hypothesis, we will pursue three specific aims. These are:
1. To determine how binding cooperativity, supercoiling, and the presence of nucleosomes, affect the equilibrium distribution of AGT among available DNA sites and between O6-alkylguanine - containing and lesion-free sequences.
2. To identify amino acids that are present at the protein-protein interface in the cooperative AGT-DNA complex. To test the consequences of mutation of these residues on DNA binding in vitro and on DNA repair, in vitro and in vivo.
3. To identify the roles played by cooperative binding, supercoiling, and nucleosomes in the kinetic mechanisms of lesion-search by AGT and on its rate of DNA repatr.
At the conclusion of this research, we will have identified the role played by cooperative binding in lesion-search, -binding and -repair, and we will have tested the notion that the rate of lesion-search depends on the structure of the DNA template. Together, these results will test the hypothesis that differences in DNA structure and accessibility determine the mechanism(s) by which AGT scans the genome for lesions and repairs them.
描述(由申请人提供):我们的目标是阐明DNA修复蛋白执行其基本生物学功能的机制。作为近期目标,我们将研究人0 6-烷基鸟嘌呤-DNA烷基转移酶(AGT)与含0 6-烷基鸟嘌呤(病变)和无病变DNA的相互作用。AGT修复DNA中的前致突变O -烷基鸟嘌呤残基。它与DNA的结合具有很大的协同性,但对序列或碱基组成的依赖性很小。这些结果反对强烈依赖于序列的靶识别机制。另一种可能性,其中包括本申请的中心假设,是合作DNA结合和访问DNA调节AGT的结合分布和DNA修复的速度。为了验证这一假设,我们将追求三个具体目标。这些是:
1.确定结合协同性、超螺旋和核小体的存在如何影响AGT在可用DNA位点之间以及含O 6-烷基鸟嘌呤和无损伤序列之间的平衡分布。
2.鉴定AGT-DNA协同复合物中存在于蛋白质-蛋白质界面的氨基酸。测试这些残基突变对体外DNA结合以及体外和体内DNA修复的影响。
3.探讨协同结合、超螺旋和核小体在AGT损伤搜索动力学机制中的作用及其对DNA修复率的影响。
在这项研究的结论,我们将确定合作绑定在病变搜索,结合和修复中发挥的作用,我们将测试的概念,病变搜索的速度取决于DNA模板的结构。总之,这些结果将检验DNA结构和可及性的差异决定AGT扫描基因组病变并修复它们的机制的假设。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Michael G. Fried其他文献
Quaternary Interactions and DNA Twist Modulate the Cooperative Binding of AGT
- DOI:
10.1016/j.bpj.2017.11.488 - 发表时间:
2018-02-02 - 期刊:
- 影响因子:
- 作者:
Michael G. Fried;Manana Melikishvili - 通讯作者:
Manana Melikishvili
The <em>Escherichia coli</em> Cyclic AMP Receptor Protein Forms a 2:2 Complex with RNA Polymerase Holoenzyme, <em>in Vitro</em>
- DOI:
10.1074/jbc.m110554200 - 发表时间:
2002-05-24 - 期刊:
- 影响因子:
- 作者:
Damian Dyckman;Michael G. Fried - 通讯作者:
Michael G. Fried
(his)6-Tag-Specific Optical Probes For Analyses of Proteins and Their Interactions
- DOI:
10.1016/j.bpj.2009.12.345 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Chunxia Zhao;Lance M. Hellman;Xin Zhan;Sidney W. Whiteheart;Michael G. Fried - 通讯作者:
Michael G. Fried
Histidine-Tag-Specific Optical Probes for Analytical Ultracentrifugation Analysis
- DOI:
10.1016/j.bpj.2011.11.2650 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Heather E. Elverson;Lance M. Hellman;Manana Melikishvili;Chunxia Zhao;Sidney W. Whiteheart;Michael G. Fried - 通讯作者:
Michael G. Fried
Substrate Interactions of a Human DNA Alkyltransferase
- DOI:
10.1016/j.bpj.2011.11.2660 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Michael G. Fried;Ingrid Tessmer;Manana Melikishvili - 通讯作者:
Manana Melikishvili
Michael G. Fried的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Michael G. Fried', 18)}}的其他基金
THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY
ARF-P53 肿瘤抑制信号通路
- 批准号:
8363758 - 财政年份:2011
- 资助金额:
$ 5.61万 - 项目类别:
THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY
ARF-P53 肿瘤抑制信号通路
- 批准号:
8169752 - 财政年份:2010
- 资助金额:
$ 5.61万 - 项目类别:
THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY
ARF-P53 肿瘤抑制信号通路
- 批准号:
7957391 - 财政年份:2009
- 资助金额:
$ 5.61万 - 项目类别:
THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY
ARF-P53 肿瘤抑制信号通路
- 批准号:
7724198 - 财政年份:2008
- 资助金额:
$ 5.61万 - 项目类别:
THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY
ARF-P53 肿瘤抑制信号通路
- 批准号:
7601844 - 财政年份:2007
- 资助金额:
$ 5.61万 - 项目类别:
THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY
ARF-P53 肿瘤抑制信号通路
- 批准号:
7369087 - 财政年份:2006
- 资助金额:
$ 5.61万 - 项目类别:
THE ARF-P53 TUMOR SUPPRESSOR SIGNALING PATHWAY
ARF-P53 肿瘤抑制信号通路
- 批准号:
7181004 - 财政年份:2005
- 资助金额:
$ 5.61万 - 项目类别:
相似海外基金
DNA glycosylases involved in interstrand crosslink repair and antibiotic self-resistance
DNA糖基化酶参与链间交联修复和抗生素自身抗性
- 批准号:
2341288 - 财政年份:2024
- 资助金额:
$ 5.61万 - 项目类别:
Standard Grant
Strategies for next-generation flavivirus vaccine development
下一代黄病毒疫苗开发策略
- 批准号:
10751480 - 财政年份:2024
- 资助金额:
$ 5.61万 - 项目类别:
Oral pathogen - mediated pro-tumorigenic transformation through disruption of an Adherens Junction - associated RNAi machinery
通过破坏粘附连接相关的 RNAi 机制,口腔病原体介导促肿瘤转化
- 批准号:
10752248 - 财政年份:2024
- 资助金额:
$ 5.61万 - 项目类别:
Understanding the Mechanisms and Consequences of Basement Membrane Aging in Vivo
了解体内基底膜老化的机制和后果
- 批准号:
10465010 - 财政年份:2023
- 资助金额:
$ 5.61万 - 项目类别:
CAREER: Uncovering Mechanisms of DNA-protein Crosslink Repair
职业:揭示 DNA-蛋白质交联修复机制
- 批准号:
2335208 - 财政年份:2023
- 资助金额:
$ 5.61万 - 项目类别:
Continuing Grant
Deciphering the mechanics of microtubule networks in mitosis
破译有丝分裂中微管网络的机制
- 批准号:
10637323 - 财政年份:2023
- 资助金额:
$ 5.61万 - 项目类别:
Mechanistic investigation into Frizzled-2 signaling for treatment of Osteogenesis Imperfecta
Frizzled-2 信号传导治疗成骨不全症的机制研究
- 批准号:
10680236 - 财政年份:2023
- 资助金额:
$ 5.61万 - 项目类别:
Defining the mechanisms by which NuMA drives spindle mechanical robustness
定义 NuMA 驱动主轴机械稳健性的机制
- 批准号:
10677401 - 财政年份:2023
- 资助金额:
$ 5.61万 - 项目类别:
An Engineered Hydrogel Platform to Improve Neural Organoid Reproducibility for a Multi-Organoid Disease Model of 22q11.2 Deletion Syndrome
一种工程水凝胶平台,可提高 22q11.2 缺失综合征多器官疾病模型的神经类器官再现性
- 批准号:
10679749 - 财政年份:2023
- 资助金额:
$ 5.61万 - 项目类别:
Biology the initiator: Harnessing Reactive Oxygen Species for Biocompatible Polymerization
生物学引发者:利用活性氧进行生物相容性聚合
- 批准号:
10667740 - 财政年份:2023
- 资助金额:
$ 5.61万 - 项目类别:














{{item.name}}会员




