Molecular Mechanisms of DNA repair in Deinococcus radiodurans

耐辐射奇球菌 DNA 修复的分子机制

• 批准号: RGPIN-2018-05980
• 负责人: Junop, Murray
• 金额: $ 4.23万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744082
• 关键词: Molecular; Mechanisms; DNA; repair; Deinococcus

DNA Double-strand breaks represent the most lethal form of damage in the genome, resulting in genetic loss and/or chromosomal re-arrangement if not properly repaired. Sources of ionizing radiation (IR) responsible for such damage include cosmic radiation, radon and the decay of radioactive material left over from nuclear weapons testing and spent nuclear fuel generated during power production. Not surprisingly, tolerable levels of exposure to such ionizing radiation are exceedingly small for all forms of life. One notable exception is the bacterium Deinococcus radiodurans. Deinococcus is able to withstand a dose of ionizing radiation 1500 times greater than humans can survive and one that would obliterate the E. coli genome 10 times over [Battista 1997]. Remarkably, despite being shattered into hundreds of small DNA fragments, Deinococcus radiodurans readily reassembles a functional genome. This feat has been attributed to the combination of a number of protective mechanisms including the presence of multiple genome copies, characteristic genome structure, and known or novel DNA repair mechanisms. Although traditional repair mechanisms appear to be active in D. radiodurans, the speed and accuracy of repair displayed are inconsistent with all previously characterized pathways [Cox 2005]. The goal of our research is to understand how uncharacterized proteins, implicated in DNA repair, function to permit the amazing DNA repair/assembly capabilities of Deinococcus radiodurans. Understanding the DNA repair strategies utilized to resist extreme IR damage is not only fascinating from a scientific point of view, but also carries great potential for practical utility. Deinococci are of interest for application in bioremediation of toxins from radioactive contaminated environments generated through processing of nuclear fuel [Appukuttan 2006]. In addition, NASA is exploring these organisms with the idea of eventually using information gained to increase protection form cosmic radiation during prolonged space travel. The greatest impact, however, that understanding (and exploiting) DNA repair/assembly capabilities of D. radiodurans resides in the area of synthetic biology. The next frontier in biological sciences is, without doubt, the ability to engineer chromosomes at the truly synthetic level. A major challenge to such endeavours is the ability to efficiently and accurately assemble large, chromosome-sized DNA molecules - Deinococci are well equipped to overcome this limitation.

DNA双链断裂是基因组中最致命的损伤形式，如果不正确修复，会导致遗传丢失和/或染色体重排。 造成这种损害的电离辐射源包括宇宙辐射、氡和核武器试验遗留下来的放射性物质的衰变以及发电过程中产生的乏核燃料。 毫不奇怪，对所有生命形式来说，暴露于这种电离辐射的可容忍水平都非常小。 一个值得注意的例外是耐辐射异常球菌。 异常球菌能够承受的电离辐射剂量是人类生存剂量的1500倍，这种剂量的辐射可以消灭大肠杆菌。大肠杆菌基因组的10倍[Battista 1997]。 值得注意的是，尽管被粉碎成数百个小的DNA片段，但耐辐射奇球菌很容易重组功能基因组。 这一壮举归因于多种保护机制的结合，包括多个基因组拷贝的存在、特征基因组结构以及已知或新型的DNA修复机制。 虽然传统的修复机制在D.对于耐放射性药物，显示的修复速度和准确性与所有先前表征的途径不一致[考克斯2005]。 我们研究的目标是了解与DNA修复有关的未表征蛋白质如何发挥作用，以允许耐辐射球菌具有惊人的DNA修复/组装能力。 理解用于抵抗极端红外损伤的DNA修复策略不仅从科学的角度来看是迷人的，而且具有巨大的实用潜力。 异常球菌在核燃料加工过程中产生的放射性污染环境中毒素的生物修复中具有重要应用[Appukuttan 2006]。 此外，美国宇航局正在探索这些生物体，最终利用获得的信息在长时间的太空旅行中增加对宇宙辐射的保护。然而，最大的影响是理解（和利用）D。抗辐射剂属于合成生物学领域。 毫无疑问，生物科学的下一个前沿是在真正的合成水平上设计染色体的能力。 这种努力的一个主要挑战是有效和准确地组装大的染色体大小的DNA分子的能力-异常球菌很好地克服了这一限制。