Modifications of newly synthesized histones and the cellular response to DNA replication stress

新合成组蛋白的修饰和细胞对 DNA 复制应激的反应

• 批准号: RGPIN-2019-05082
• 负责人: Wurtele, Hugo
• 金额: $ 3.64万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738054
• 关键词: Modifications; newly; synthesized; histones; cellular

A broad spectrum of chemical or physical agents present in the environment can damage the genetic material of cells (DNA) and impair its functions. Indeed, DNA damage can lead to the inactivation or misregulation of important genes and ultimately cause cells to die or to behave aberrantly. Fortunately, cells possess efficient DNA repair mechanisms that allow them to mitigate the deleterious consequences of genetic lesions. In order to fit in the tiny confines of the cell, DNA is packaged into a structure called chromatin. Cells can chemically modify the basic building blocks of chromatin, which are proteins called "histones", to influence their functions. Our research program aims to use baker's yeast as a model organism to understand how chemical modifications of histone proteins influence DNA repair. We anticipate that a better understanding of these fundamental processes will unearth novel links between specific determinants of chromatin structure and the response to environmental DNA-damaging agents. Importantly, these processes generally operate in analogous manners in yeast and human cells. Our research is therefore ultimately expected to provide important clues as to the function of chromatin in maintaining the integrity of human genetic material.

环境中存在的广泛的化学或物理物质会破坏细胞的遗传物质(DNA)并损害其功能。的确，DNA损伤会导致重要基因的失活或失控，最终导致细胞死亡或行为异常。幸运的是，细胞拥有有效的DNA修复机制，使它们能够减轻遗传损伤的有害后果。为了适应细胞的微小范围，DNA被包装成一种称为染色质的结构。细胞可以通过化学修饰染色质的基本成分，也就是被称为“组蛋白”的蛋白质，来影响它们的功能。我们的研究项目旨在以面包酵母为模式生物，了解组蛋白的化学修饰如何影响DNA修复。我们预计，对这些基本过程的更好理解将发现染色质结构的特定决定因素与对环境DNA损伤剂的反应之间的新联系。重要的是，这些过程通常在酵母和人类细胞中以类似的方式运行。因此，我们的研究最终有望为染色质在维持人类遗传物质完整性方面的功能提供重要线索。