Repair of localized DNA damage

修复局部DNA损伤

• 批准号: 7592051
• 负责人: Michael Seidman
• 金额: $ 27.25万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 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/7592051
• 关键词: Antigens; Cell Respiration; Cells; Crosslinker; DNA; DNA Damage; DNA lesion; Ficusin; Genetic Transcription; Incubated; Individual; Laser Microscopy; Life; Link; Localized; Monitor; Pharmaceutical Preparations; Proteins; Psoralens; Site; Technology; adduct; chemotherapy; crosslink; interest; photoactivation; repaired; response

Interstrand crosslinks are particularly dangerous DNA lesions as they are absolute blocks to replication and transcription. They are believed to occur as a product of oxidative metabolism, and are also a consequence of treatment with some chemotherapy drugs. Psoralens are photoactive DNA interstrand crosslinkers that have been used clinically for many years. We synthesized, and demonstrated the activity of, antigen linked psoralens. Photoactivation of defined subnuclear regions in cells incubated with the compounds resulted in localized crosslinks. Repair of these adducts was followed in repair proficient and deficient cells. We are using this approach to follow the recruitment of proteins into sites of crosslink repair.

链间交联是特别危险的DNA损伤，因为它们是复制和转录的绝对障碍。它们被认为是氧化代谢的产物，也是某些化疗药物治疗的结果。光活性DNA链间交联剂已在临床上使用多年。我们合成了抗原连接的peptiens，并证明了其活性。 与化合物孵育的细胞中确定的亚核区域的光活化导致局部交联。 这些加合物的修复在修复熟练和缺陷细胞中进行。我们正在使用这种方法来跟踪蛋白质进入交联修复位点的募集。