DNA SEARCH AND BASE FLIPPING MECHANISMS OF DNA GLYCOSYLASE, MUTM

DNA 糖基化酶 MUTM 的 DNA 搜索和碱基翻转机制

• 批准号: 8169233
• 负责人: GREGORY Lawrence VERDINE
• 金额: $ 0.35万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169233
• 关键词: Bacterial DNA; Base Excision Repairs; Catalysis; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Damage; DNA glycosylase; Disulfides; Funding; Genome; Grant; Guanine; Institution; Lesion; Light; Pathway interactions; Proteins; Rare Lesion; Research; Research Personnel; Resources; Site; Source; United States National Institutes of Health; base; computer studies; crosslink; nucleobase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. MutM is a bacterial DNA glycosylase that specifically recognizes oxidatively damaged DNA bases and initiates the base excision repair pathway. Given the subtle conformational differences in the lesion base, 8-oxoguanine, and normal DNA base, guanine, and the scarcity of the lesions, a fundamental question arises: how does MutM locate the rare lesion sites among the vast genome? In addition, base flipping, an essential step for DNA glycosylase catalysis, is not well understood, and whether protein is actively promoting base extrusion is currently in debate. Using the disulfide crosslinking strategy, we have covalently trapped ordinarily transient intermediates during the search by MutM for lesions during nucleobase extrusion. These intermediates not only shed light on the mechanism of lesion recognition and catalysis, but have also provided valuable starting points for our computational studies of the base extrusion pathway.

这个子项目是众多研究子项目之一