UNDERSTANDING THE BROAD SUBSTRATE SPECIFICITY OF ALKA AT THE ATOMIC LEVEL

在原子水平上了解 ALKA 的广泛底物特异性

• 批准号: 8361670
• 负责人: GREGORY Lawrence VERDINE
• 金额: $ 0.29万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361670
• 关键词: Affect; Apoptosis; Base Excision Repairs; Base Pairing; Biochemistry; Cancer Etiology; Cell Cycle Progression; Cells; Charge; Chemistry; DNA; DNA Repair; DNA biosynthesis; DNA lesion; Enzymes; Excision; Funding; Genetic Recombination; Genetic Transcription; Genome; Grant; Left; Lesion; Modification; Mutation; National Center for Research Resources; Needles; Nucleotides; Pathway interactions; Principal Investigator; Process; Research; Research Infrastructure; Resources; Source; Substrate Specificity; System; Toxic Environmental Substances; United States National Institutes of Health; base; cost; non-genomic; nucleobase; repair enzyme; repaired; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Inside cells, DNA is under constant attack by exogenous environmental toxins and cellular metabolites, insults that can produce various covalent nucleobase modifications. Left uncorrected, these lesions can cause mutations affecting nearly all aspects of genome function, including transcription, DNA replication and recombination, and also non-genomic processes such as cell cycle progression and apoptosis. The mutations that result from cellular mismanagement of such lesions are the cause of cancer. To counter the threat posed by DNA lesions, all cells have evolved repair mechanisms charged with the responsibility for locating damaged nucleotides and correcting them. Most single base modifications in DNA are corrected by enzymes (glycosylases) of the base excision repair pathway (BER). Even before the base excision process can begin, however, the repair enzymes must interrogate millions of base pairs of undamaged DNA in order to locate one damaged nucleobase; a classic needle in the haystack problem. This exhaustive full genome search presents a truly formidable task for the DNA repair system, which must evolve enzymes that can track down lesions with exceptional accuracy and efficiency. This subproject utilizes a combination of chemistry, biochemistry, and structural biology to better understand how the enzymes of the BER identify DNA lesions within the vast excess of normal DNA, as well as the mechanisms of the enzymatic repair of such lesions.

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