权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular basis for repairing DNA double-strand breaks by non homologous end-joining

非同源末端连接修复DNA双链断裂的分子基础

基本信息

批准号：
BB/J018643/1
负责人：
Aidan Doherty
金额：
$ 86.07万
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=BB%2FJ018643%2F1
关键词：
Molecular basis repairing DNA double

项目摘要

Our cells contain DNA, the so called "genetic blueprint of life" which encodes the information for our genes. DNA has a simple repeating structure composed of two complementary strands of DNA which form a double-helix structure. The integrity of DNA is constantly being challenged by various DNA-damaging agents. These agents include high energy UV and X-ray radiation from the sun, chemicals both man-made and environmental and even the oxygen we breathe can attack and damage DNA. In recent years it has been realised that our own cells produce a large number of proteins responsible for repairing this DNA damage which, if left unchecked, would lead to the development of conditions such as cancer. These protein "machines" can cut out and replace aberrant DNA mutations/structures and splice together broken DNA strands. One such protein is called DNA ligase, which interacts with its partner proteins: Ku , polymerase and nuclease to form a DNA break repair complex. This repair apparatus is able to detect physical breaks in the DNA helices, bring the ends back together, remodel them if required and, finally, reseal these breaks to restore the continuity of the double-strand DNA. The focus of this work is to understand how these repair complexes can bridge the break and make the DNA ends come back together prior to the sealing step.

我们的细胞含有DNA，即所谓的“生命的遗传蓝图”，它为我们的基因编码信息。DNA具有简单的重复结构，由两条互补的DNA链组成，形成双螺旋结构。DNA的完整性不断受到各种DNA破坏剂的挑战。这些物质包括来自太阳的高能紫外线和X射线辐射，人造和环境的化学物质，甚至我们呼吸的氧气都可以攻击和破坏DNA。近年来，人们已经意识到，我们自己的细胞产生大量的蛋白质，负责修复这种DNA损伤，如果不加以控制，将导致癌症等疾病的发展。这些蛋白质“机器”可以切割和替换异常的DNA突变/结构，并将断裂的DNA链拼接在一起。一种这样的蛋白质被称为DNA连接酶，它与它的伴侣蛋白质：Ku，聚合酶和核酸酶相互作用，形成DNA断裂修复复合物。这种修复装置能够检测DNA螺旋中的物理断裂，将末端重新连接在一起，如果需要的话，重新改造它们，最后，重新密封这些断裂以恢复双链DNA的连续性。这项工作的重点是了解这些修复复合物如何弥合断裂，并使DNA末端在密封步骤之前重新结合在一起。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An archaeal family-B DNA polymerase variant able to replicate past DNA damage: occurrence of replicative and translesion synthesis polymerases within the B family.

DOI：
10.1093/nar/gku683
发表时间：
2014-09
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Jozwiakowski SK;Keith BJ;Gilroy L;Doherty AJ;Connolly BA
通讯作者：
Connolly BA

Ribosomal oxygenases are structurally conserved from prokaryotes to humans.

DOI：
10.1038/nature13263
发表时间：
2014-06-19
期刊：
Nature
影响因子：
64.8
作者：
Chowdhury R;Sekirnik R;Brissett NC;Krojer T;Ho CH;Ng SS;Clifton IJ;Ge W;Kershaw NJ;Fox GC;Muniz JRC;Vollmar M;Phillips C;Pilka ES;Kavanagh KL;von Delft F;Oppermann U;McDonough MA;Doherty AJ;Schofield CJ
通讯作者：
Schofield CJ

A non-canonical mismatch repair pathway in prokaryotes.

DOI：
10.1038/ncomms14246
发表时间：
2017-01-27
期刊：
Nature communications
影响因子：
16.6
作者：
Castañeda-García A;Prieto AI;Rodríguez-Beltrán J;Alonso N;Cantillon D;Costas C;Pérez-Lago L;Zegeye ED;Herranz M;Plociński P;Tonjum T;García de Viedma D;Paget M;Waddell SJ;Rojas AM;Doherty AJ;Blázquez J
通讯作者：
Blázquez J

Primase-polymerases are a functionally diverse superfamily of replication and repair enzymes.