DNA Excision Repair and DNA Damage Checkpoints

DNA 切除修复和 DNA 损伤检查点

• 批准号: 8640182
• 负责人: AZIZ SANCAR
• 金额: $ 61.27万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8640182
• 关键词: Animal Model; Biochemical; Biochemical Pathway; Biochemistry; Biological Assay; Biological Models; Brain; Cell Cycle; Cells; Checkpoint kinase 1; Chemical Agents; Circadian Rhythms; Complex; Coupling; DNA; DNA Damage; DNA damage checkpoint; Data; Development; Dose-Rate; Excision Repair; Exhibits; Exposure to; Funding; Genetic Models; Genome Stability; Genotoxic Stress; Goals; Grant; Human; In Vitro; Incidence; Investigation; Link; Liver; Malignant Neoplasms; Mammalian Cell; Mammals; Measures; Mediating; Modeling; Molecular; Mus; Nucleotide Excision Repair; Pathway interactions; Periodicity; Pharmaceutical Preparations; Phosphotransferases; Proteins; Public Health; Recommendation; Regulation; Research; Research Infrastructure; Research Personnel; Resolution; Scheme; Set protein; Signal Pathway; Signal Transduction; Skin; Skin Cancer; Source; Sunlight; System; Testing; Time; Tissues; Translational Research; UV induced; UV induced DNA damage; Ultraviolet Rays; Work; abstracting; base; biochemical model; cancer prevention; cancer therapy; carcinogenicity; chromatin immunoprecipitation; circadian pacemaker; coping; design; in vivo; irradiation; mimetics; novel; nuclease; programs; reconstitution; repaired; research study; response; sunlight-induced; transcription factor; treatment strategy; ultraviolet irradiation; vector

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT DNA EXCISION REPAIR AND DNA DAMAGE CHECKPOINTS Nucleotide excision repair and DNA damage checkpoints are two major cellular responses to DNA damage that are essential for genomic stability. The goal of our research is to understand the molecular mechanisms of these systems and to use this information to develop cancer prevention and treatment strategies. To accomplish this goal we will perform the following experiments. Aim 1. Nucleotide Excision Repair and Skin Cancer Development as a Function of the Circadian Clock. Our studies on the regulation of nucleotide excision repair in mammals have revealed that excision repair exhibits high amplitude oscillation with a daily periodicity in most mouse tissues. We will analyze the daily variability of excision repair of UV photoproducts in skin and determine whether this variability is associated with carcinogenicity of UV light delivered at different times of the day. The results of this study will enable us to make specific recommendations to lower the incidence of skin cancer induced by sunlight and other UV sources. Aim 2. Biochemical Analysis of the UV-Induced DNA Damage Checkpoint. We will purify and characterize the proteins involved in ATR kinase-mediated DNA damage checkpoint response which is the primary checkpoint pathway activated by UV and UV-mimetic chemical agents. We will reconstitute this checkpoint system from highly purified components in vitro and analyze the coupling of nucleotide excision repair with the ATR checkpoint signaling pathway. Understanding this DNA damage signaling pathway should facilitate the design of novel chemotherapeutic approaches to treat cancer.

描述（由申请人提供）：