Dissecting SUMO Activating Enzyme Pathways to Inform Therapy

一个细胞通过将染色体中的DNA分裂成两个子细胞而变成两个细胞。这个过程是由一种微小的蛋白质支持的，这种蛋白质被添加到其他蛋白质中，以帮助包正确分裂。正确的DNA分裂在某些癌症中尤为重要，这些癌症是由一种叫做Myc扩增的特殊基因变化驱动的。阻止这种小蛋白质添加的新药似乎对杀死具有这种基因变化的癌症很有用。我们最近发现，这些药物的靶点以令人惊讶的方式发挥作用。我们发现它至少有两种不同的功能，而不是像以前认为的那样只有一个角色；其中之一是帮助DNA在分裂成子细胞时保持完好无损的鲜为人知的过程。我们在这个项目中的目标是研究药物靶点如何以这些不同的方式发挥作用，找出其中哪一种对支持癌细胞存活最重要，并发现它如何防止DNA损伤。这项工作对如何使用新药来帮助癌症患者具有启示意义。

One cell becomes two by dividing its DNA, in packets of chromosomes, into two daughter cells. This process is supported by a tiny protein that is added to other proteins to help the packets divide correctly. Correct DNA division is particularly important in some cancers that are driven by a particular genetic change, called Myc amplification. New drugs that stop the small protein from being added appear to be useful in killing cancers that have this genetic change. We have recently discovered that the target of those drugs behaves in surprising ways. Instead of having a single role as previously thought, we find it has at least two different functions; one of these is in the poorly understood process of helping DNA remain undamaged as it is divided into the daughter cells. Our aims in this project are to investigate how the drug target behaves in these different ways, to find out which one of them is most important in supporting cancer cell survival, and to discover how it works to prevent DNA damage. This work has implications for how the new drugs are used to help cancer patients.