DNA-Protein cross-links: cellular effects and repair mechanisms
DNA-蛋白质交联:细胞效应和修复机制
基本信息
- 批准号:9441806
- 负责人:
- 金额:$ 36.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-05-21 至 2019-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityAgingAlkylating AgentsAntineoplastic AgentsBiologicalBiological AssayBrainBypassCancer BiologyCarcinogensCardiovascular DiseasesCell Culture TechniquesCell DeathCellsChemicalsCircular DNAConflict (Psychology)DNADNA RepairDNA Repair GeneDNA biosynthesisDNA lesionDNA-Directed DNA PolymeraseDNA-Protein InteractionDataDependenceDevelopmentEnvironmental PollutantsEvaluationExcisionExposure toFree RadicalsGeneticGenetic EngineeringGenetic RecombinationGenetic TranscriptionGenomeGoalsGuanineHeartHeart DiseasesHumanIn VitroIonizing radiationLeadLesionLipid PeroxidationLiteratureMalignant NeoplasmsMammalian CellMass Spectrum AnalysisMechlorethamineMetabolicMethodologyMolecularMolecular and Cellular BiologyMutagenesisMutationNatureNucleotide Excision RepairOccupationalOrganic SynthesisOutcomePathway interactionsPharmaceutical PreparationsPlasmidsPlatinum CompoundsPlayPositioning AttributePropertyProtein EngineeringProteinsReactive Oxygen SpeciesResearchRoleSiteStructureSystemTestingTimeTissuesToxic Environmental SubstancesToxic effectToxinTranscription-Coupled RepairTransition ElementsUltraviolet RaysXenobioticsYeastsadductage relatedage related neurodegenerationanticancer activityantitumor drugbasechemotherapeutic agentclinically relevantcrosslinkcytotoxiccytotoxicityerythritol anhydrideexperimental studygenotoxicityhomologous recombinationhuman DNAhuman diseaseinsightirradiationnovelpublic health relevancerecombinational repairrepairedsynthetic construct
项目摘要
DESCRIPTION (provided by applicant): DNA-protein cross-links (DPCs) are super-bulky, helix-distorting DNA lesions that result from exposure to a variety of chemical and physical agents such as antitumor drugs, environmental/ occupational toxins, ionizing radiation, and endogenous free radical-generating systems. Due to their unusually bulky nature, DPCs are hypothesized to interfere with normal DNA-protein interactions required for DNA replication, transcription, and repair, potentially leading to mutagenesis, genotoxicity, and cytotoxicity. However, the biological outcomes of DPC lesions in cells are poorly understood because of their inherent structural complexity and the difficulty of generating DNA substrates containing structurally defined DPC for biological evaluation. Our long-term goal is to elucidate the role tha spontaneous and induced DPCs play in human disease and in the anticancer activity of common chemotherapeutic agents. The objectives of this application are to determine the biological consequences of DPC formation in human cells and to discover the mechanism(s) responsible for the removal of DPCs from DNA. Our studies will for the first time systematically examine the influence of DPCs on DNA repair and replication. Our central hypothesis is that, if not repaired, DPCs exert mutagenic and cytotoxic effects, significantly contributing to the biological effects of many known carcinogens and antitumor drugs. Collectively, these studies will provide significant new insights into the molecular and cellular biology of DPCs and are expected to fundamentally advance the fields of DNA repair, cancer biology, and molecular mechanisms of aging.
描述(申请人提供):DNA-蛋白质交叉链接(DPC)是一种超大的、扭曲螺旋的DNA损伤,由于暴露于各种化学和物理因素,如抗肿瘤药物、环境/职业毒素、电离辐射和内源性自由基生成系统。由于DPC异常庞大的性质,它们被认为会干扰DNA复制、转录和修复所需的正常DNA-蛋白质相互作用,可能导致突变、遗传毒性和细胞毒性。然而,由于DPC损伤固有的结构复杂性,以及产生含有结构定义的DPC的DNA底物用于生物学评价的困难,人们对DPC损伤在细胞中的生物学结果知之甚少。我们的长期目标是阐明自发和诱导的DPC在人类疾病中所起的作用,以及在常见化疗药物的抗癌活性中的作用。这项应用的目的是确定在人类细胞中形成DPC的生物学后果,并发现负责从DNA中去除DPC的机制(S)。我们的研究将首次系统地研究DPC对DNA修复和复制的影响。我们的中心假设是,如果不修复,DPC会发挥诱变和细胞毒作用,显著促进许多已知致癌物和抗肿瘤药物的生物学效应。总的来说,这些研究将为DPC的分子和细胞生物学提供重要的新见解,并有望从根本上推动DNA修复、癌症生物学和衰老的分子机制领域的发展。
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 }}
COLIN R CAMPBELL其他文献
COLIN R CAMPBELL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('COLIN R CAMPBELL', 18)}}的其他基金
DNA Protein Cross-Links:Cellular Effects and Repair Mechanisms
DNA 蛋白质交联:细胞效应和修复机制
- 批准号:
10428509 - 财政年份:2014
- 资助金额:
$ 36.98万 - 项目类别:
DNA-Protein cross-links: cellular effects and repair mechanisms
DNA-蛋白质交联:细胞效应和修复机制
- 批准号:
8759022 - 财政年份:2014
- 资助金额:
$ 36.98万 - 项目类别:
DNA Protein Cross-Links:Cellular Effects and Repair Mechanisms
DNA 蛋白质交联:细胞效应和修复机制
- 批准号:
10626876 - 财政年份:2014
- 资助金额:
$ 36.98万 - 项目类别:
DNA Protein Cross-Links:Cellular Effects and Repair Mechanisms
DNA 蛋白质交联:细胞效应和修复机制
- 批准号:
9816926 - 财政年份:2014
- 资助金额:
$ 36.98万 - 项目类别:
DNA Protein Cross-Links:Cellular Effects and Repair Mechanisms
DNA 蛋白质交联:细胞效应和修复机制
- 批准号:
10017995 - 财政年份:2014
- 资助金额:
$ 36.98万 - 项目类别:
DNA Protein Cross-Links:Cellular Effects and Repair Mechanisms
DNA 蛋白质交联:细胞效应和修复机制
- 批准号:
10713474 - 财政年份:2014
- 资助金额:
$ 36.98万 - 项目类别:
DNA Protein Cross-Links:Cellular Effects and Repair Mechanisms
DNA 蛋白质交联:细胞效应和修复机制
- 批准号:
10163054 - 财政年份:2014
- 资助金额:
$ 36.98万 - 项目类别:
Summer Research Training at the University of Minnesota Medical School
明尼苏达大学医学院暑期研究培训
- 批准号:
7802239 - 财政年份:2007
- 资助金额:
$ 36.98万 - 项目类别:
Summer Research at the University of Minnesota Medical School
明尼苏达大学医学院暑期研究
- 批准号:
10418721 - 财政年份:2007
- 资助金额:
$ 36.98万 - 项目类别:
Summer Research Training at the University of Minnesota Medical School
明尼苏达大学医学院暑期研究培训
- 批准号:
7269095 - 财政年份:2007
- 资助金额:
$ 36.98万 - 项目类别:
相似海外基金
Interplay between Aging and Tubulin Posttranslational Modifications
衰老与微管蛋白翻译后修饰之间的相互作用
- 批准号:
24K18114 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The Canadian Brain Health and Cognitive Impairment in Aging Knowledge Mobilization Hub: Sharing Stories of Research
加拿大大脑健康和老龄化认知障碍知识动员中心:分享研究故事
- 批准号:
498288 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Operating Grants
EMNANDI: Advanced Characterisation and Aging of Compostable Bioplastics for Automotive Applications
EMNANDI:汽车应用可堆肥生物塑料的高级表征和老化
- 批准号:
10089306 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Collaborative R&D
Baycrest Academy for Research and Education Summer Program in Aging (SPA): Strengthening research competencies, cultivating empathy, building interprofessional networks and skills, and fostering innovation among the next generation of healthcare workers t
Baycrest Academy for Research and Education Summer Program in Aging (SPA):加强研究能力,培养同理心,建立跨专业网络和技能,并促进下一代医疗保健工作者的创新
- 批准号:
498310 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Operating Grants
関節リウマチ患者のSuccessful Agingに向けたフレイル予防対策の構築
类风湿性关节炎患者成功老龄化的衰弱预防措施的建立
- 批准号:
23K20339 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Life course pathways in healthy aging and wellbeing
健康老龄化和福祉的生命历程路径
- 批准号:
2740736 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Studentship
NSF PRFB FY 2023: Connecting physiological and cellular aging to individual quality in a long-lived free-living mammal.
NSF PRFB 2023 财年:将生理和细胞衰老与长寿自由生活哺乳动物的个体质量联系起来。
- 批准号:
2305890 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Fellowship Award
I-Corps: Aging in Place with Artificial Intelligence-Powered Augmented Reality
I-Corps:利用人工智能驱动的增强现实实现原地老龄化
- 批准号:
2406592 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Standard Grant
McGill-MOBILHUB: Mobilization Hub for Knowledge, Education, and Artificial Intelligence/Deep Learning on Brain Health and Cognitive Impairment in Aging.
McGill-MOBILHUB:脑健康和衰老认知障碍的知识、教育和人工智能/深度学习动员中心。
- 批准号:
498278 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Operating Grants
Welfare Enhancing Fiscal and Monetary Policies for Aging Societies
促进老龄化社会福利的财政和货币政策
- 批准号:
24K04938 - 财政年份:2024
- 资助金额:
$ 36.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)