Structure of the Smc5-6 DNA repair and chromosome maintenance protein complex

遗传物质(DNA)的准确遗传是所有生物生存的关键。DNA必须在细胞分裂前复制(复制)，但DNA碱基受损等障碍可能会导致复制过程中出现问题。细胞已经发展出不同的方法来消除这种障碍(修复)，如果DNA损伤不能被去除，它可以在DNA复制期间或之后立即绕过(耐受)。当复制DNA时，修复或耐受性的失败可能会导致错误。这些错误会导致永久性的基因变化，进而可能导致癌症发病率的增加。许多蛋白质参与修复和耐受。我们已经研究了几年的Smc5-6就是其中之一，它是一种大型蛋白质复合体？有八个组件。我们建议结合我们四个研究小组的专业知识来确定这个综合体的三维结构。这将使我们能够了解不同的成分是如何结合在一起的，它们各自做什么，以及它们如何帮助完成细胞中蛋白质复合体的功能。这将帮助我们了解Smc6是如何保护我们免受DNA复制过程中DNA损伤造成的问题的。这项工作对普通人群中癌症和老龄化的发展具有重要意义。

The accurate inheritance of the genetic material (DNA) is key to the survival of all organisms. DNA has to be copied (replicated) before cells divide but obstacles such as damaged DNA bases can lead to problems during the copying process. Cells have developed different ways to remove such obstacles (repair), and if the DNA damage cannot be removed it can be bypassed, either during or immediately after DNA copying (tolerance). Failure of repair or tolerance can result in errors when the DNA is copied. These errors cause permanent genetic changes, which in turn can result in increased cancer incidence. Many proteins are involved in repair and tolerance. One of these, Smc5-6, which we have been studying for several years, is a big ?protein complex? with eight components. We propose to combine the expertise of our four research groups to determine the 3-dimensional structure of this complex. This will enable us to understand how the different components fit together, what they each do, and how they help to fulfil the functions of the protein complex in the cell. This will help us to understand how Smc6 acts to protect us from the problems caused by DNA damage during DNA copying. This work has implications for the development of cancer and aging in the general population.