STRUCTURES OF DNA REPAIR ENZYME DNA COMPLEXES

DNA修复酶在维持基因组中起着关键作用 所有活细胞的完整性。他们负责检测和 切除DNA中可能出现的突变损伤 自发地或通过氧化损伤。详细、高分辨率 这些酶及其DNA复合体的X射线晶体结构， 将提供坚实的基础来理解 基本修复过程的生物分支。DNA修复 这项提议的主题是人类尿嘧啶脱氧核糖核酸 糖基酶(UDG)，我们收集了几个高分辨率(&gt；2.0 E)野生型和突变型人类UDG的数据集 SSRL光束线7-1处含有尿嘧啶的双链DNA。决心 在原子细节中揭示的这些结构中UDG的基础 初始DNA损伤检测的特异性和建议的模型。

DNA repair enzymes play a key role in maintaining the genonmic integrity of all living cells. They are responsible for detecting and excising the potentially mutagenic lesions that arise in DNA either spontaneously or via oxidative damage. Detailed, high-resolution X-ray crystal structures of these enzymes, and their DNA complexes, will provide a solid basis towards understanding the mechanistic and biologic ramifications of essential repair processes. The DNA repair enzyme that is the subject of this proposal is human uracil-DNA glycosylase (UDG), and we have collected several high-resolution (>2.0 E) data sets of both wild-type and mutant human UDG bound to uracil-containing duplex DNA at SSRL beamline 7-1. The determination of these structures revealed in atomic detail the basis for UDG specificity and suggested models for initial DNA damage detection.