DNA RESTRICTION DAMAGE AND REPAIR

DNA 限制性损伤和修复

• 批准号: 2634598
• 负责人: STUART M LINN
• 金额: $ 29.67万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2634598
• 关键词: DNA damage; DNA repair; Escherichia coli; NAD(H) phosphate; bacterial genetics; chemical models; computer simulation; electron microscopy; enzyme mechanism; free radical oxygen; high performance liquid chromatography; hydrogen peroxide; iron; laboratory rat; mass spectrometry; mitochondrial DNA; nuclear magnetic resonance spectroscopy; nucleic acid sequence; oligonucleotides; oxidative stress; tissue /cell culture; ultraviolet radiation

DESCRIPTION: The long-term objective of this work is to understand how oxygen radicals damage DNA and thus destroy the genetic integrity of the cell, and to learn how the cell responds to such stress. Genetic, biochemical and now chemical studies have shown that toxicity by H2O2, O2.-, O2 may arise largely through iron- mediated Fenton reactions that generate oxyradicals that resemble, but are not identical to, diffusible hydroxyl radicals, and that DNA is perhaps the major target of these radicals. In essence, Fe+2 reacts with H2O2 to form the damaging radical and Fe+3, then NADH reduces the Fe+3 back to Fe+2. The goals during the next grant period will be I) to study further the role(s) of NAD(P)H in these processes in vivo and in vitro; II) to understand the basis of sequence preferences for DNA damage by iron and peroxide and how iron interacts with DNA with some emphasis upon telomeres; III) to study the role of O2 in Fe/H2O2/DNA chemistry; IV) to complete inventories of DNA base damage during these processes; and V) to study levels of oxidative damage in mitochondrial DNA in steady state and H2O2-stress conditions. It is the contention of the principal investigator that these studies should help to clarify the basis of degenerative and other disease states brought about by oxygen radicals, and also help to design regimens to treat and prevent such disease processes.

描述：这项工作的长期目标是了解如何 氧自由基损害DNA，从而破坏 细胞，并了解细胞如何应对这种压力。 遗传， 生化和现在的化学研究表明，H2O2，O2.-， O2可能主要通过产生的铁介导的芬顿反应而产生 类似但与扩散羟基不同但不相同的草自由基 自由基，而DNA也许是这些自由基的主要靶标。 在 本质，Fe+2与H2O2反应形成破坏性的自由基和Fe+3，然后 NADH将Fe+3减少到Fe+2。 下一个赠款期间的目标 将是i）进一步研究NAD（p）h在这些过程中的作用 体内和体外； ii）了解序列偏好的基础 铁和过氧化物的DNA损伤以及铁如何与某些DNA相互作用 强调端粒； iii）研究O2在Fe/H2O2/DNA中的作用 化学; iv）在这些过程中完成DNA基本损害的清单 过程； v）研究线粒体DNA中氧化损伤的水平 在稳定状态和H2O2压力条件下。 这是 这些研究应有助于阐明基础的主要研究者 由氧自由基带来的退化性和其他疾病状态 还有助于设计治疗和预防这种疾病的方案 过程。