Cellular Responses to DNA Damage

细胞对 DNA 损伤的反应

• 批准号: 10706918
• 负责人: Peggy Hsieh
• 金额: $ 47.37万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706918
• 关键词: Apoptosis; Apoptotic; Atomic Force Microscopy; Biochemical; Cell Cycle Arrest; Cell Cycle Progression; Cell Death; Cells; Chemical Agents; Collaborations; Complex; DNA; DNA Damage; DNA Repair Pathway; Genome Stability; Goals; Human; Individual; Libraries; Mammalian Cell; Methods; Mismatch Repair; Molecular; Molecular Conformation; Monitor; Normal Cell; Nuclear Envelope; Pharmaceutical Preparations; Proteins; Replication Error; Reporter; Resistance; Signal Transduction; Small Molecule Chemical Library; System; high throughput screening; patient population; response; screening

The goal of this project is to understand at a molecular level the ways in which the DNA mismatch repair system corrects replication errors and how mammalian cells respond to DNA damage. In collaboration with Dr. Dorothy Erie, UNC-Chapel Hill, we have used atomic force microscopy and biochemical approaches to examine the conformations of individual protein-DNA complexes. We have developed a cell reporter system to screen for cell cycle arrest and apoptosis in high-throughput assays of small molecule chemical libraries. We hope this reporter system will yield important new information in early rounds of library screening for apoptotic agents.

该项目的目标是在分子水平上了解DNA错配修复系统纠正复制错误的方式以及哺乳动物细胞如何应对DNA损伤。 与北卡罗来纳大学教堂山分校的多萝西伊利博士合作，我们使用原子力显微镜和生物化学方法来检查单个蛋白质-DNA复合物的构象。 我们已经开发了一种细胞报告系统，用于在小分子化学文库的高通量测定中筛选细胞周期停滞和凋亡。 我们希望这个报告系统将产生重要的新信息，在早期几轮的图书馆筛选凋亡剂。

项目成果

DNA mismatch repair: Dr. Jekyll and Mr. Hyde?

• DOI: 10.1016/j.molcel.2012.08.020
• 发表时间: 2012-09-14
• 期刊: MOLECULAR CELL
• 影响因子: 16
• 作者: Hsieh, Peggy

DNA mismatch repair and the DNA damage response.

• DOI: 10.1016/j.dnarep.2015.11.019
• 发表时间: 2016-02
• 期刊: DNA repair
• 影响因子: 3.8
• 作者: Li Z;Pearlman AH;Hsieh P
• 通讯作者: Hsieh P

EGFR inhibits DNA mismatch repair.

EGFR 抑制 DNA 错配修复。

• DOI: 10.1073/pnas.1505168112
• 发表时间: 2015
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Hsieh,Peggy;Pearlman,AlexanderH
• 通讯作者: Pearlman,AlexanderH