TARGETED DNA REPAIR OF PSORALEN ADDUCTS IN SKIN CELLS

这个项目的重点是DNA修复引起的序列特异性损伤 人皮肤中与反义寡核苷酸(PSO-AGOS)相连的补骨脂素 细胞。长期目标是阐明dna的结构因素。 它一般控制着它的修复，转录偶联修复 很特别。本研究将专门针对L)论证具体的 PSO-AGOS和PSO-AGOS对皮肤细胞的基因抑制作用 紫外线(UVA)；2)表征靶向损伤 并决定随后的细胞修复如何 根据基因中的特定序列或位置而变化；3)确定DNA是否 在一个地点维修会影响到另一个地点的维修；以及4)使用系统 分化角质形成细胞以进一步研究转录 控制修复。 这项研究将在设备齐全的 菲利普·C·哈纳瓦特教授，他与人共同发现了30多岁的切除修复 几年前，其实验室继续在 DNA修复领域。实验室小组、院系和大学 环境由充足和杰出的智力和技术组成 支持。研究经验将使应聘者学到 成为一名独立生物医学医生的关键概念和技能 科学家。因此，该奖项将作为接受初级学生的准备 教师在皮肤科学术中的地位并领导一个具有竞争力的 与皮肤相关的光生物学和光医学研究进展 疾病。

This project focuses on DNA repair of sequence-specific damage caused by psoralens linked to antigene oligonucleotides (pso-AGOs) in human skin cells. The long-term goal is to elucidate the structural factors of DNA which govern its repair in general, and transcription-coupled repair in particular. The research will specifically aim l) To demonstrate specific gene suppression in skin cells caused by treatment with pso-AGOs and ultraviolet A light (UVA); 2) To characterize the targeted damage produced by these agents and determine how the subsequent cellular repair varies with specific sequences or sites in a gene; 3) To determine if DNA repair at one site influences repair at another; and 4) To use a system of differentiating keratinocytes to examine further how transcription controls repair. The research will be executed in the fully equipped laboratory of Professor Philip C. Hanawalt who co-discovered excision repair over 30 years ago and whose laboratory continues to do pioneering work in the field of DNA repair. The laboratory group, departmental and university environments consists of ample and outstanding intellectual and technical support. The research experience will allow the candidate to learn concepts and skills crucial to becoming an independent biomedical scientist. The award will thus serve as preparation to assume a junior faculty position in academic dermatology and to lead a competitive research effort in photobiology and photomedicine related to cutaneous diseases.