Molecular Mechanism of Mammalian DNA Excision Repair, DNA Damage Checkpoints and the Circadian Clock
哺乳动物 DNA 切除修复、DNA 损伤检查点和生物钟的分子机制
基本信息
- 批准号:9895813
- 负责人:
- 金额:$ 98.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-01 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimalsAntineoplastic AgentsAreaBiochemistryBiophysicsCellular biologyCouplingDNADNA DamageDNA damage checkpointDiseaseDrug ScreeningExcision RepairGeneticGoalsHealthHumanHuman GenomeIn VitroLeadLinkMapsMethodsMolecularNucleotide Excision RepairNucleotidesPhysiologyRegulationResearchResolutionSystemValidationWorkbasecancer preventioncancer therapycarcinogenicitycircadian pacemakerhuman DNAimprovedinnovationnovel strategiespublic health relevancereconstitution
项目摘要
DESCRIPTION (provided by applicant): We work on three inter-related subjects: mammalian DNA excision repair, DNA damage checkpoints, and the circadian clock. We have made a number of recent discoveries in all three areas that lead to deeper understanding of the interconnections between these three systems and are directly relevant to human health and disease treatment. We developed the XR-seq (excision Repair-sequencing) method to generate an excision repair map of the entire human genome at single nucleotide resolution; we have reconstituted an in vitro system that links nucleotide excision repair to the DNA damage checkpoint; and we have discovered regulation of excision repair by the circadian clock and developed novel approaches to understand the molecular mechanism of the mammalian circadian clock. We will apply these new conceptual and technical advances for the following objectives: (1) understand factors that affect excision repair of DNA damage by carcinogenic and by anticancer agents, (2) improve the in vitro system of excision repair-checkpoint coupling for potential use in anticancer drug screening and validation, and (3) characterize the molecular mechanism of the mammalian circadian clock and develop strategies of cancer prevention and cancer treatment based on clock control of human DNA excision repair activity. This approach is innovative because it combines biochemistry/biophysics, cell biology, genetics and animal physiology to understand the mechanistic basis and connections between mammalian DNA excision repair, DNA damage checkpoints, and of the circadian clock. The proposed research is significant because of its relevance to cancer prevention and treatment.
描述(由申请人提供):我们研究三个相互关联的主题:哺乳动物DNA切除修复,DNA损伤检查点和生物钟。我们最近在这三个领域都取得了一些发现,加深了对这三个系统之间相互联系的理解,并与人类健康和疾病治疗直接相关。我们开发了XR-seq(切除修复测序)方法,以单核苷酸分辨率生成整个人类基因组的切除修复图谱;我们重建了一个将核苷酸切除修复与DNA损伤检查点联系起来的体外系统;我们发现了生物钟对切除修复的调节,并开发了新的方法来了解哺乳动物生物钟的分子机制。我们将把这些新的概念和技术进步应用于以下目标:(1)了解影响致癌剂和抗癌剂引起的DNA损伤的切除修复的因素,(2)改进切除修复-检查点偶联的体外系统以用于抗癌药物筛选和验证,以及(3)表征哺乳动物生物钟的分子机制,并基于人类DNA切除修复活性的时钟控制开发癌症预防和治疗策略。这种方法是创新的,因为它结合了生物化学/生物物理学,细胞生物学,遗传学和动物生理学,以了解哺乳动物DNA切除修复,DNA损伤检查点和生物钟之间的机制基础和联系。这项拟议中的研究意义重大,因为它与癌症预防和治疗有关。
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 }}
AZIZ SANCAR其他文献
AZIZ SANCAR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('AZIZ SANCAR', 18)}}的其他基金
DNA Adduct Detection and Repair in Mammalian Cells
哺乳动物细胞中 DNA 加合物的检测和修复
- 批准号:
10653232 - 财政年份:2021
- 资助金额:
$ 98.01万 - 项目类别:
DNA Adduct Detection and Repair in Mammalian Cells
哺乳动物细胞中 DNA 加合物的检测和修复
- 批准号:
10299723 - 财政年份:2021
- 资助金额:
$ 98.01万 - 项目类别:
Molecular Mechanism of Mammalian DNA Excision Repair and the Circadian Clock
哺乳动物DNA切除修复和生物钟的分子机制
- 批准号:
10687262 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
Molecular Mechanism of Mammalian DNA Excision Repair and the Circadian Clock
哺乳动物DNA切除修复和生物钟的分子机制
- 批准号:
10799054 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
Molecular Mechanism of Mammalian DNA Excision Repair and the Circadian Clock
哺乳动物DNA切除修复和生物钟的分子机制
- 批准号:
10458623 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
Single Nucleotide Resolution Map of Formation and Repair of Bulky Adducts in the Human Genome
人类基因组中大体积加合物的形成和修复的单核苷酸解析图
- 批准号:
9322347 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
Single Nucleotide Resolution Map of Formation and Repair of Bulky Adducts in the Human Genome
人类基因组中大体积加合物的形成和修复的单核苷酸解析图
- 批准号:
9186286 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
Molecular Mechanism of Mammalian DNA Excision Repair, DNA Damage Checkpoints and the Circadian Clock
哺乳动物 DNA 切除修复、DNA 损伤检查点和生物钟的分子机制
- 批准号:
9251831 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
Molecular Mechanism of Mammalian DNA Excision Repair, DNA Damage Checkpoints and the Circadian Clock
哺乳动物 DNA 切除修复、DNA 损伤检查点和生物钟的分子机制
- 批准号:
9071163 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
Single Nucleotide Resolution Map of Formation and Repair of Bulky Adducts in the Human Genome
人类基因组中大体积加合物的形成和修复的单核苷酸解析图
- 批准号:
9976511 - 财政年份:2016
- 资助金额:
$ 98.01万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 98.01万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 98.01万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 98.01万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 98.01万 - 项目类别:
Discovery Early Career Researcher Award
Zootropolis: Multi-species archaeological, ecological and historical approaches to animals in Medieval urban Scotland
Zootropolis:苏格兰中世纪城市动物的多物种考古、生态和历史方法
- 批准号:
2889694 - 财政年份:2023
- 资助金额:
$ 98.01万 - 项目类别:
Studentship
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 98.01万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 98.01万 - 项目类别:
Training Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 98.01万 - 项目类别:
Continuing Grant
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 98.01万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 98.01万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)