Physiological constraints on DNA replication and fidelity

DNA 复制和保真度的生理限制

• 批准号: RGPIN-2016-03658
• 负责人: Scott, Matthew
• 金额: $ 2.26万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708407
• 关键词: Physiological; constraints; DNA; replication; fidelity

The blueprint of life is encoded in the DNA of an organism; this genetic program dictates what molecules will be produced in order to sustain growth and reproduction of the organism. The replication, repair, and (in some cases) damage of the bacterial genome is dependent upon the activity of specific proteins in the cell. What is remarkable is that the abundance of these proteins changes depending upon how rapidly the organism grows. Consequently, we expect a heretofore unexplored intrinsic and complex coupling between genome stability and cell growth. Our objective is to determine how the success of the growth program affects the fidelity of transmitting that program to subsequent generations. Over the past several decades, investigators have elucidated the molecular mechanisms underlying genetic maintenance and repair, although these mechanisms have been studied largely isolated from the physiological context of a growing organism. Our lab has recently formulated fundamental growth laws' that characterize constraints on resource allocation in growing bacteria. The resulting framework provides a means to interface molecular mechanisms with the growth-demands of the organism. Unraveling the interplay between growth physiology and genetic stability has important consequences for how we understand speciation and diversification, as well as informing clinical practice in the eradication of pathogenic infections.

生命的蓝图被编码在生物体的DNA中;这个遗传程序决定了为了维持生物体的生长和繁殖而产生什么样的分子。细菌基因组的复制，修复和（在某些情况下）损伤取决于细胞中特定蛋白质的活性。值得注意的是，这些蛋白质的丰度取决于生物体生长的速度。因此，我们预期基因组稳定性和细胞生长之间存在着迄今尚未探索的内在和复杂的耦合。我们的目标是确定增长计划的成功如何影响将该计划传递给后代的保真度。 在过去的几十年里，研究人员已经阐明了遗传维持和修复的分子机制，尽管这些机制在很大程度上是从生长有机体的生理环境中分离出来的。我们的实验室最近制定了基本的生长规律，描述了生长细菌中资源分配的限制。由此产生的框架提供了一种手段接口的分子机制与生长的有机体的需求。 揭示生长生理学和遗传稳定性之间的相互作用对于我们如何理解物种形成和多样化以及为根除病原性感染的临床实践提供信息具有重要意义。