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

点击翻译按钮获取中文摘要

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.