Analysis of RNA polymerase fidelity and its implications for cellular function
Analysis of RNA polymerase fidelity and its implications for cellular function
批准号:
7658860
负责人:
MIGUEL GARCIA-DIAZ
金额:
$24.4万
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-07-16 至 2011-05-31
关键词:
AddressAffectAgingAging-Related ProcessAllelesAlzheimer&aposs DiseaseAmyloid beta-Protein PrecursorBiologicalBiological AssayBypassCell physiologyCellsCoupledDNA DamageDNA lesionDNA-Directed RNA PolymeraseDepositionDevelopmentDiseaseDisease ProgressionDown SyndromeEnvironmentEnvironmental ExposureEnzymesEtiologyEventExposure toFrequenciesGenesGenetic TranscriptionGoalsHot SpotHumanLesionLinkMeasurementMeasuresMitochondriaMitochondrial RNAMolecularMolecular GeneticsMutagenesisMutationNeurodegenerative DisordersNeuronsPathologyPatientsPredispositionProcessProtein BiosynthesisProtein PrecursorsProteinsRNARNA PhagesRNA PrecursorsRNA chemical synthesisResearchRiskStructureSystemTestingTranscriptYeastsbasedisorder riskenvironmental agenthuman UBB proteinin vivomutantnormal agingpolymerizationtoxic metal
中文摘要
这个项目计划检查RNA聚合酶的保真度,以及这种保真度是如何通过
环境因素,并影响疾病和衰老的进展。抄本!错误被认为是
是细胞功能的病理改变的基础。例如,泛素-B和(Jamyloid)的错误转录
前体蛋白在神经元中被检测到,其产物积累在
阿尔茨海默氏症和唐氏综合症患者。这些产物的积累与疾病的进展有关,
并被认为与该病的病因学有关。这项建议将探讨其准确性
RNA聚合酶的合成及其在环境中暴露于不同试剂后的变化。一个
综合保真度分析将用于在广泛的范围内确定聚合错误率
测序背景,并检查是否存在可能使某些基因处于危险之中的突变热点。
结构-功能研究将解决RNA聚合酶错误的基础,目的是识别容易出错的错误
等位基因来分析低转录保真度在体内的后果。该项目将提供一个
详细表征了RNA聚合酶的保真度,并考察了它们之间的关系
环境暴露和转录保真度可以调节对某些疾病或非病理性疾病的易感性
衰老的过程。
-基因转录是蛋白质合成的第一步。这项研究探索了基因的准确性。
转录,这种准确性是如何被环境调节的,以及这种准确性的变化可能是如何
对细胞有害。了解基因转录的准确性与基因转录的关系
环境暴露是评估其在疾病进展和衰老过程中的影响的关键。
英文摘要
This project proposes to examine RNA polymerase fidelity, and how this fidelity is modulated by
environmental agents and influences the progression of disease and aging. Transcriptions! errors are thought
to underlie pathological alterations in cellular function. For instance, faulty transcripts of ubiquitin-B and (Jamyloid
precursor protein are detected in neurons and their products accumulate in protein deposits of
Alzheimer's and Down's syndrome patients. Accumulation of these products is linked to disease progression,
and has been postulated to be implicated in the etiology of the disease. This proposal will probe the accuracy
of synthesis by RNA polymerases, and its alteration by environmental exposure to different agents. A
comprehensive fidelity assay will be used to determine polymerization error rates over a broad range of
sequence contexts and examine the existence of mutational hot spots that might put certain genes at risk.
Structure-function studies will address the basis of RNA polymerase errors with the aim of identifying errorprone
alleles to analyze the in vivo consequences of low transcription fidelity. This project will provide a
detailed characterization of RNA polymerase fidelity and examine how the relationship between
environmental exposures and transcription fidelity can modulate susceptibility to certain diseases or the nonpathological
process of aging.
-Gene transcription is the first step in the synthesis of proteins. This research explores the accuracy of gene
transcription, how this accuracy is modulated by the environment and how alterations of this accuracy can be
detrimental to the cell. Understanding the connection between the accuracy of gene transcription and
environmental exposures is key to assess its influence in the progression of disease and aging.
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会议论文
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批准号:8371513
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项目类别:
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资助金额:$29.65万
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财政年份:2012
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
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资助金额:$29.83万
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财政年份:2012
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依托单位:
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批准号:8363393
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项目类别:
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资助金额:$0.94万
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财政年份:2011
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
TRANSCRIPTION FACTOR A, MITOCHONDRIAL
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批准号:8363355
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项目类别:
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资助金额:$0.46万
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财政年份:2011
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
TRANSCRIPTION FACTOR A, MITOCHONDRIAL
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批准号:8170589
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项目类别:
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资助金额:$0.63万
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财政年份:2010
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
1,4-DIHYDROXY-2-NAPHTHOYL-COA SYNTHASE IN COMPLEX WITH HIGH AFFINITY SUBSTRATE A
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批准号:8170660
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项目类别:
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资助金额:$0.54万
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财政年份:2010
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
Analysis of RNA polymerase fidelity and its implications for cellular function
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批准号:7847663
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项目类别:
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资助金额:$24.34万
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财政年份:2008
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
Analysis of RNA polymerase fidelity and its implications for cellular function
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批准号:7618316
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项目类别:
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资助金额:$24.53万
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财政年份:2008
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
Training Program in Pharmacological Sciences
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批准号:10162607
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项目类别:
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资助金额:$33.39万
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财政年份:1977
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负责人:MIGUEL GARCIA-DIAZ
-
依托单位:
Training Grant in Pharmacological Sciences (T32GM007518) Supplement
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批准号:9062131
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项目类别:
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资助金额:$8.64万
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财政年份:1977
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
Training grant in Pharmacological Sciences
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批准号:8878269
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项目类别:
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资助金额:$29.96万
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财政年份:1977
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
Training Program in Pharmacological Sciences
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批准号:9208924
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项目类别:
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资助金额:$33.32万
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财政年份:1977
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
Training grant in Pharmacological Sciences
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批准号:9102229
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项目类别:
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资助金额:$22.09万
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财政年份:1977
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负责人:MIGUEL GARCIA-DIAZ
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依托单位:
海外基金