Quantitative Adductomics Approaches for Assessing the Occurrence and Repair of DNA Adducts

用于评估 DNA 加合物的发生和修复的定量加合物组学方法

• 批准号: 10172860
• 负责人: Yinsheng Wang
• 金额: $ 35.57万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-16 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172860
• 关键词: Acetylcysteine; Affect; Cancer Biology; Coupled; Cultured Cells; Cytosine; DNA; DNA Adduction; DNA Adducts; DNA Damage; DNA Repair; DNA Repair Enzymes; DNA biosynthesis; DNA lesion; DNA photoproducts; Development; Dilution Techniques; Environmental Exposure; Enzymes; Epigenetic Process; Etiology; Excision; Exposure to; Family; Gene Expression Regulation; Genetic Fingerprintings; Genetic Transcription; Human; Induced Mutation; Lead; Left; Lipid Peroxidation; Malignant Neoplasms; Mammalian Cell; Measurement; Mediating; Metabolism; Methods; Methylation; Modification; Molecular; Mus; Mutagens; Outcome; Play; Positioning Attribute; Prevention; Preventive; Process; Publishing; Reactive Oxygen Species; Research; Risk Factors; Role; Skin; Skin Cancer; Skin Tissue; Source; Specimen; Sunscreen Effect; Sunscreening Agents; Therapeutic; Tissues; Topical application; UV induced; Ultraviolet Rays; Veins; analytical method; animal tissue; base; cancer chemoprevention; cancer initiation; cancer prevention; cancer risk; cancer therapy; epigenetic regulation; genetic information; genetic manipulation; human disease; melanoma; methyl group; novel; oxidation; repaired; skin cancer prevention; stable isotope; sunlight-induced; ultraviolet irradiation

The long-term objective of this application is to discover and characterize the adductomics-based exposure indicators for the assessment of cancer risks and for cancer prevention. Endogenous metabolism and environmental exposure can both give rise to DNA damage. If left unrepaired, the resulting DNA adducts may compromise the flow of genetic information by inhibiting DNA replication and transcription and inducing mutations in these processes. In addition, the ultimate levels of DNA adducts accumulated in mammalian cells and tissues are the result of a dynamic interplay between DNA adduct formation and repair. Thus, it is important to establish a robust analytical method for the quantitative measurement of a broad range of DNA adducts that are implicated in the etiology for the development of cancer and other human diseases. Such a method will also enable the characterizations of the repair of DNA adducts, which may lead to the discovery of risk factors for cancer initiation and development, and guide the development of approaches for effective cancer chemoprevention. In this application, we propose to establish a DNA adductomic approach by employing and expanding our recently established LC-MS/MS methods for the quantification of DNA adducts induced by reactive oxygen species, DNA photoproducts arising from UV irradiation, and DNA epigenetic marks, which represent a substantial subset of the DNA adductome. We will then employ this adductomic approach for investigating the modulations of the levels of oxidatively induced DNA lesions and DNA epigenetic marks by DNA repair enzymes, for assessing the implications of DNA adducts in the etiology of melanoma development, and for evaluating the effects of sunscreen components on altering UV-induced DNA adduct formation. The proposed research will have a long- lasting impact on the fields of DNA damage repair and cancer biology by offering a facile adductomic platform for characterizing the risk factors and therapeutic/preventive approaches that modulate the formation and removal of DNA adducts.

该应用程序的长期目标是发现和表征内收切开术为基础的暴露

项目成果

GLOBAL AND TARGETED PROFILING OF GTP-BINDING PROTEINS IN BIOLOGICAL SAMPLES BY MASS SPECTROMETRY.

• DOI: 10.1002/mas.21637
• 发表时间: 2021-05
• 期刊: Mass spectrometry reviews
• 影响因子: 6.6
• 作者: Huang M;Wang Y
• 通讯作者: Wang Y

Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases.

• DOI: 10.1021/acs.jproteome.2c00225
• 发表时间: 2022-08-05
• 期刊: JOURNAL OF PROTEOME RESEARCH
• 影响因子: 4.4
• 作者: Miao, Weili;Yin, Jiekai;Porter, Douglas F.;Jiang, Xiaogang;Khavari, Paul A.;Wang, Yinsheng
• 通讯作者: Wang, Yinsheng

Targeted Proteomic Analysis Revealed Kinome Reprogramming during Acquisition of Radioresistance in Breast Cancer Cells.

靶向蛋白质组学分析表明，在乳腺癌细胞中采集放射线抗性期间的Kinome重编程。

• DOI: 10.1021/acs.jproteome.1c00075
• 发表时间: 2021-05-07
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Miao W;Bade D;Wang Y
• 通讯作者: Wang Y

Chemical Proteomic Profiling of the Interacting Proteins of Isoprenoid Pyrophosphates.

• DOI: 10.1021/acs.analchem.0c01676
• 发表时间: 2020-05
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Rong Cai;Xuejiao Dong;Kailin Yu;Xiaomei He;Xiaochuan Liu;Yinsheng Wang

Bypassing a 8,5'-cyclo-2'-deoxyadenosine lesion by human DNA polymerase η at atomic resolution.

人类 DNA 聚合酶 γ 在原子分辨率下绕过 8,5-环-2-脱氧腺苷损伤。

• DOI: 10.1073/pnas.1812856115
• 发表时间: 2018
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Weng,PeterJ;Gao,Yang;Gregory,MarkT;Wang,Pengcheng;Wang,Yinsheng;Yang,Wei
• 通讯作者: Yang,Wei