CAREER: The Formation and Repair of Oxidative Damage in Nucleosome Core Particles

点击翻译按钮获取中文摘要

Free radicals and even oxygen itself can, under the right conditions, damage genomic DNA. One major consequence of this assault is the formation of mutagenic lesions derived from the four native nucleobases of DNA. Therefore, there exists a critical need to understand the chemical reactions leading to the formation of these oxidative lesions, the structural consequences of these lesions in duplex DNA, and the dynamics of repair processes responsible for the removal these lesions from the genome. Previous work has focused primarily upon analyzing these processes in isolated DNA duplexes. DNA in the eukaryotic nucleus is not isolated, but tightly packaged by histone proteins into chromatin. The binding of DNA to a histone core particle forms a nucleosome, the fundamental building block of chromatin. Dramatic changes in DNA structure and accessibility to solvent are induced upon nucleosome formation. Any or all of these structural changes could impact oxidative damage formation, propagation, and repair in DNA. The first objective of this project is to define how packaging DNA into a nucleosome perturbs processes related to the formation of oxidized nucleobase lesions. Second, this project will quantify the efficiency and rates of DNA repair at the surface of nucleosome core particles. This project will enhance both graduate and undergraduate education through laboratory research designed and carried out predominantly by graduate students and minority summer undergraduate research associates recruited from selected four-year colleges and universities.