Defining the molecular link between DNA repair and chromatin remodelling

定义 DNA 修复和染色质重塑之间的分子联系

• 批准号: BB/G001723/1
• 负责人: Christopher West
• 金额: $ 44.16万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG001723%2F1
• 关键词: Defining; molecular; link; between; DNA

This study investigates how plants detect, signal and repair DNA damage. DNA is essential for growth and reproduction but is constantly being damaged by highly reactive chemicals present in the cell and environmental factors including carcinogens, UVB and soil pollutants such as heavy metals. A single DNA double strand break is sufficient to cause cell death and DNA therefore needs to be continuously repaired if the organism is to survive. The first steps in repair are detection and signalling of DNA damage. It is important that the cell rapidly recognises and signals the presence of DNA damage to minimise the harmful effects on growth and development of the organism. In this study, to be undertaken at the Faculty of Biological Sciences, University of Leeds, we will establish how DNA double strand breaks are detected and repaired using the model plant Arabidopsis thaliana. We will build on our existing knowledge of DNA damage and repair in plants, including exciting recent results that show that the primary detector of DNA damage, termed the MRN complex, interacts with proteins responsible for the modification of histones (proteins that package DNA and regulate its accessibility). This novel result suggests a mechanism by which the cell can signal DNA damage by modifying histones at the site of the break in the very early stages of DNA damage detection and repair. In this proposal, we will test this hypothesis that histone modification plays a crucial early role in DNA repair. We have isolated mutant plants lacking our newly identified histone modifying proteins, and in this study we will see if DNA breaks are processed differently, in terms of histone modification, the rate of repair and the 'unpacking' of DNA. We will also determine the effects of these mutations on the ability of plants to withstand DNA damage. It is important that we understand these signalling processes in plants, as DNA damage signalling and repair is required to allow growth of crop plants in conditions of environmental stress, and failure of these pathways will result in reduced yields and the accumulation of deleterious mutations in future generations. In view of climate change, it is now important that we understand how plants respond to environmental stresses, which will impact on crop survival and yield. As many of the processes are conserved amongst different organisms, these studies may also have important implications for cancer, aging and gene therapy.

这项研究调查了植物如何检测、发出信号并修复 DNA 损伤。 DNA 对于生长和繁殖至关重要，但经常受到细胞中存在的高反应性化学物质和环境因素（包括致癌物、UVB 和重金属等土壤污染物）的损害。单个DNA双链断裂就足以导致细胞死亡，因此如果生物体要生存，DNA就需要不断修复。修复的第一步是检测 DNA 损伤并发出信号。重要的是，细胞能够快速识别 DNA 损伤并发出信号，以尽量减少对生物体生长和发育的有害影响。在这项由利兹大学生物科学学院进行的研究中，我们将确定如何使用模式植物拟南芥检测和修复 DNA 双链断裂。我们将建立在植物 DNA 损伤和修复的现有知识基础上，包括令人兴奋的最新结果，这些结果表明 DNA 损伤的主要检测器（称为 MRN 复合物）与负责组蛋白修饰的蛋白质（包装 DNA 并调节 DNA 的蛋白质）相互作用。其可访问性）。这一新颖的结果提出了一种机制，在 DNA 损伤检测和修复的早期阶段，细胞可以通过修饰断裂位点的组蛋白来发出 DNA 损伤信号。在本提案中，我们将检验组蛋白修饰在 DNA 修复早期发挥关键作用的假设。我们分离出了缺乏新发现的组蛋白修饰蛋白的突变植物，在这项研究中，我们将了解 DNA 断裂在组蛋白修饰、修复速率和 DNA“解包”方面是否有不同的处理方式。我们还将确定这些突变对植物抵抗 DNA 损伤的能力的影响。我们了解植物中的这些信号传导过程非常重要，因为作物植物在环境胁迫条件下生长需要 DNA 损伤信号传导和修复，而这些途径的失败将导致未来产量下降和有害突变的积累几代人。鉴于气候变化，现在重要的是我们了解植物如何应对环境压力，这将影响作物的生存和产量。由于许多过程在不同的生物体中是保守的，这些研究也可能对癌症、衰老和基因治疗具有重要意义。

项目成果

Arabidopsis TAF1 is an MRE11-interacting protein required for resistance to genotoxic stress and viability of the male gametophyte.

拟南芥 TAF1 是一种 MRE11 相互作用蛋白，是抵抗遗传毒性应激和雄性配子体活力所必需的。

• DOI: 10.1111/tpj.13020
• 发表时间: 2015-11
• 期刊: The Plant journal : for cell and molecular biology
• 作者: Waterworth WM;Drury GE;Blundell-Hunter G;West CE
• 通讯作者: West CE

Repairing breaks in the plant genome: the importance of keeping it together.

• DOI: 10.1111/j.1469-8137.2011.03926.x
• 发表时间: 2011-12
• 期刊: The New phytologist
• 作者: W. Waterworth;G. Drury;C. M. Bray;C. E. West