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

Smc5-6 DNA 修复和染色体维持蛋白复合物的结构

基本信息

批准号：
G1001668/1
负责人：
Laurence Pearl
金额：
$ 87.47万
依托单位：
University of Sussex
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=G1001668%2F1
关键词：
Structure Smc5 DNA repair chromosome

项目摘要

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.

遗传物质（DNA）的准确遗传是所有生物生存的关键。在细胞分裂之前，DNA必须被复制（复制），但在复制过程中，诸如DNA碱基受损等障碍可能会导致问题。细胞已经开发出不同的方法来消除这些障碍（修复），如果DNA损伤不能被消除，它可以被绕过，无论是在DNA复制过程中或之后立即（耐受）。当DNA被复制时，修复或耐受的失败可能导致错误。这些错误会导致永久性的遗传变化，从而导致癌症发病率增加。许多蛋白质参与修复和耐受。其中之一，Smc 5 -6，我们已经研究了几年，是一个大的？蛋白质复合物有八个组成部分。我们建议联合收割机我们四个研究小组的专业知识，以确定这个复杂的三维结构。这将使我们能够了解不同的组分如何组合在一起，它们各自做什么，以及它们如何帮助实现细胞中蛋白质复合物的功能。这将有助于我们了解Smc 6如何保护我们免受DNA复制过程中DNA损伤引起的问题。这项工作对一般人群中癌症和衰老的发展有影响。