Molecular insights into ubiquitin remodelling factor p97(VCP) in DNA damage response and genome stability

你的身体是由数十亿个细胞组成的，它们都必须作为一个团队工作。细胞所做的几乎每一件事都与蛋白质有关。蛋白质传递决策、构建结构、翻译遗传指令、修复损伤和传递信号。因此，癌症以蛋白质不正常工作为标志也就不足为奇了。有时蛋白质会失效，有时它们会做得太好，或者在错误的时间完成。蛋白质不断地被创造和循环，这确保了蛋白质不会老化和损坏。制造和回收蛋白质之间的平衡受到严格的检查，以确保给定蛋白质的数量恰到好处。我们的工作重点是细胞循环蛋白质的方式。我们知道，陈旧或不需要的蛋白质被标记为可回收利用的标签，称为泛素。巨大的回收机器，称为蛋白酶体，抓住泛素手柄，回收附着的蛋白质。我们不知道泛素标签何时以及如何贴上的细节。我们想知道在修复受损DNA的过程中这是如何起作用的。DNA损伤可能是癌症的起点；但它也是有效放疗和化疗的关键。如果我们知道细胞如何循环修复DNA辐射和化疗损伤的蛋白质，那么我们就能够设计出使放射和化疗更有效的方法。这笔赠款将为研究提供资金，以提高我们对DNA损伤修复所涉及的蛋白质及其循环过程的理解。

Your body is built of billions of cells, and they all have to work as a team. Almost everything a cell does involves a protein. Proteins relay decisions, build structures, translate genetic instructions, repair damage, and carry signals. So it is not surprising that cancer is marked by proteins not working properly. Sometimes the proteins fail; sometimes they do their job too well, or do it at the wrong time.Proteins are created and recycled constantly; this makes sure that proteins do not get old and damaged. The balance between making and recycling proteins is kept in tight check, making sure that the amount of a given protein is just right. Our work focuses on the way cells recycle proteins. We know that proteins that are old or not needed are labelled for recycling with a tag called ubiquitin. Huge recycling machines called proteasomes grab hold of the ubiquitin handle and recycle the attached protein. We don't know in detail when and how the ubiquitin label is attached. We want to know how this works during the process of repairing damaged DNA. Damaged DNA can be a starting point for cancer; but it's also the key to effective radio- and chemotherapy. If we knew how cells recycle the proteins that repair radiation and chemotherapeutic damage to DNA then we would be able to design ways to make radio- and chemotherapy more effective.This grant will fund research to improve our understanding of the proteins involved in DNA damage repair and the processes that recycle them.