Translesion Synthesis Opposite Carcinogen Bound DNA

跨损伤合成相反致癌物结合 DNA

• 批准号: 7270480
• 负责人: ROBERT L EOFF
• 金额: $ 4.88万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270480
• 关键词: 2' -deoxycytidine 5' -triphosphate; Address; Aging-Related Process; Amides; Base Pairing; Biochemistry; Bypass; Carcinogens; Cell Death; Cell division; Cells; Class; Collaborations; Complex; Crystallography; DNA; DNA Binding; DNA Damage; DNA Modification Process; DNA Polymerase beta; DNA biosynthesis; DNA lesion; DNA-Directed DNA Polymerase; Defense Mechanisms; Depth; Deuterium; Environment; Enzymes; Event; Exonuclease; Exposure to; Family; Fellowship; Figs - dietary; Gene Mutation; Genetic Code; Genomics; Guanine; Hydrogen; In Vitro; Individual; Kinetics; Knowledge; Lead; Lesion; Life; Light; Longevity; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Metals; Methodology; Mitosis; Modeling; Modification; Molecular Motors; Mutation; Nature; O(6)-benzylguanine; Organism; Play; Polymerase; Positioning Attribute; Process; Rate; Reaction; Research Proposals; Role; Series; Site; Source; Spectrometry; Staging; Structure; Sulfolobus solfataricus; System; Techniques; Thinking; Work; base; cancer type; carcinogenesis; day; experience; fascinate; human disease; improved; insight; interest; repaired; tumorigenesis

DESCRIPTION (provided by applicant): Our bodies are subjected to a barrage of potentially damaging agents every day. Some of these agents come from the environment surrounding us and some are generated inside us by the very act of living. Fortunately for our longevity, systems have evolved within our cells that repair much of the damage that we experience. One of the last lines of defense against permanent damage to our genetic code resides in a class of enzymes called the Y-family polymerases. These molecular motors are unique in their ability to deal with damaged DNA. However, given the veritable jungle of types of DNA lesions, there are many things that we do not yet understand concerning how the Y-family polymerases repair damage. In an effort to address the myriad of unanswered questions regarding Y-family polymerase bypass of damaged DNA, this proposal will study the ability of a model Y-family polymerase called Dpo4 to copy past a very common form of DNA damage that results from exposure to agents that are not only found in the environment but are also used in chemotherapeutic regimes to treat multiple types of cancer. Kinetic analyses will be combined with x-ray crystallographic studies in order to couple structure with function.

描述（由申请人提供）：我们的身体每天都会受到大量潜在有害物质的影响。其中一些因素来自我们周围的环境，另一些则由我们的生活行为产生。幸运的是，对于我们的长寿来说，我们的细胞内已经进化出了能够修复我们所经历的大部分损伤的系统。防止遗传密码永久受损的最后一道防线之一是一类称为 Y 家族聚合酶的酶。这些分子马达在处理受损 DNA 方面具有独特的能力。然而，考虑到 DNA 损伤类型的真正丛林，关于 Y 家族聚合酶如何修复损伤，我们尚不了解很多事情。为了解决有关 Y 家族聚合酶绕过受损 DNA 的众多悬而未决的问题，该提案将研究一种名为 Dpo4 的模型 Y 家族聚合酶复制一种非常常见的 DNA 损伤的能力，这种损伤是由于接触不仅存在于环境中而且也用于治疗多种癌症的化疗方案中的药物而引起的。动力学分析将与 X 射线晶体学研究相结合，以便将结构与功能结合起来。