Molecular genetic analysis of BRCT domain function and RhoGEF signalling in DNA-damage response and apoptosis.

DNA 损伤反应和细胞凋亡中 BRCT 结构域功能和 RhoGEF 信号传导的分子遗传学分析。

• 批准号: nhmrc : 104918
• 负责人: Prof Robert Saint
• 金额: $ 13.05万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/molecular-genetic-analysis-response-apoptosis/94976
• 关键词: Molecular; genetic; analysis; BRCT; domain

Cancers arise as a consequence of a series of genetic changes, usually by mutation of DNA. DNA is consistently exposed to an array of damaging agents, but the majority of mutations are corrected by cellular repair mechanisms. We now know that if these mechanisms work normally, too few mutations persist for cancer to result. However if these DNA damage repair mechanisms are themselves faulty, a high mutation rate occurs and a high risk of cancer results. DNA damage has another outcome. If the damage is too extensive, the cell commits suicide, not because it cannot function, but because it senses the DNA damage and chooses to die. One poorly understood aspect of the response to DNA damage is how the cell senses the damage and activates the suicide process. We have discovered a novel gene that appears to play a role in this sensing and suicide signalling process. The mouse version of this gene can itself act as a cancer-causing gene. We propose, however, to study the equivalent gene in Drosophila melanogaster, a more powerful experimental system, to characterise in detail its role in these processes. In this way we hope to generate a much more detailed understanding of the way that cells deal with DNA damage and choose suicide when the damage is too severe.

癌症是一系列基因变化的结果，通常是 DNA 突变。 DNA 始终暴露于一系列损伤剂中，但大多数突变都可以通过细胞修复机制得到纠正。我们现在知道，如果这些机制正常工作，那么持续存在的突变太少，不会导致癌症。然而，如果这些 DNA 损伤修复机制本身有缺陷，就会发生高突变率，导致患癌症的风险很高。 DNA 损伤还有另一种结果。如果损伤太广泛，细胞就会自杀，不是因为它无法发挥作用，而是因为它感觉到DNA损伤并选择死亡。 DNA 损伤反应的一个鲜为人知的方面是细胞如何感知损伤并激活自杀过程。我们发现了一种新基因，它似乎在这种感知和自杀信号传导过程中发挥作用。该基因的小鼠版本本身可以充当致癌基因。然而，我们建议研究果蝇（一个更强大的实验系统）中的等效基因，以详细描述其在这些过程中的作用。通过这种方式，我们希望能够更详细地了解细胞处理 DNA 损伤并在损伤过于严重时选择自杀的方式。