CAREER: Mechanisms and consequences of epigenome-recruited DNA repair systems in plants

职业：植物中表观基因组招募的 DNA 修复系统的机制和后果

• 批准号: 2338236
• 负责人: Grey Monroe
• 金额: $ 102.08万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-02-01 至 2029-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2338236&HistoricalAwards=false
• 关键词: CAREER; Mechanisms; consequences; epigenome; recruited

Mutations provide the necessary fuel for evolution and crop breeding but also cause diseases like cancer. Preventing harmful mutations is thus a challenge that all life must overcome. Discovering how organisms achieve this by promoting DNA repair in specific regions of their genome has emerged at the forefront of advances in human health, agriculture, and biotechnology. This NSF CAREER Award project will study newly discovered DNA repair mechanisms in plants that could help them protect critical DNA regions from mutations. This research will foster a new understanding of how organisms can use their epigenome—-in this case, chemical changes to the histone proteins around which DNA winds--to recruit DNA repair proteins, valuable for addressing multiple challenges across the life sciences. Researchers will apply state-of-the-art experimental tools to dissect how these genetic mechanisms function and their consequences on mutation. The anticipated results will also directly inform the development of next-generation genome engineering tools for crop improvement. The project's integration of research and educational outreach through the EnvironMentors program is set to enrich the learning experience of underserved high school students, fostering future generations of scientists.Epigenome-recruited DNA repair systems--fusions between DNA repair proteins and histone reader domains--serve as mechanisms to help reduce mutation rates in certain genome regions. However, our understanding of such systems beyond those described in humans remains a significant knowledge gap. This NSF CAREER Award project will spearhead the study of recently discovered plant-specific mechanisms, focusing on PDS5 and MSH6 proteins, which have Tudor histone reader domains and bind to H3K4me1 modifications. Leveraging mutant and transgenic lines, researchers will construct a comprehensive model of these systems. Their role in affecting mutation rates at molecular and phenotypic scales will be measured through large-scale mutation accumulation experiments. This mechanistic model will be further evaluated and applied through tests of improved plant genome editing methods. Integrating research with education through the EnvironMentors program will explore the consequences of these mechanisms on tolerance to environmental stress. This research will address critical questions about the function and adaptive value of epigenome-recruited DNA repair mechanisms in plants.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

突变为进化和作物育种提供了必要的燃料，但也会导致癌症等疾病。因此，防止有害突变是所有生命都必须克服的挑战。发现生物体如何通过促进基因组特定区域的DNA修复来实现这一目标，已经成为人类健康、农业和生物技术进步的前沿。这个NSF职业奖项目将研究新发现的植物DNA修复机制，帮助它们保护关键的DNA区域免受突变。这项研究将促进对生物体如何利用其表观基因组（在这种情况下，DNA围绕的组蛋白发生化学变化）来招募DNA修复蛋白的新理解，这对解决生命科学中的多重挑战很有价值。研究人员将应用最先进的实验工具来剖析这些遗传机制的功能及其对突变的影响。预期的结果也将直接为下一代作物改良基因组工程工具的开发提供信息。该项目通过环境项目将研究和教育推广相结合，旨在丰富缺乏教育的高中生的学习经验，培养未来的科学家。表观基因组招募的DNA修复系统——DNA修复蛋白和组蛋白解读域之间的融合——作为一种机制，有助于降低某些基因组区域的突变率。然而，我们对这些系统的理解超出了人类的描述，仍然是一个重大的知识差距。这个NSF CAREER奖项目将率先研究最近发现的植物特异性机制，重点研究PDS5和MSH6蛋白，它们具有Tudor组蛋白读取器结构域并结合H3K4me1修饰。利用突变和转基因系，研究人员将构建这些系统的综合模型。它们在分子和表型尺度上影响突变率的作用将通过大规模突变积累实验来测量。这一机制模型将通过改进的植物基因组编辑方法的试验进一步评估和应用。通过环境计划将研究与教育相结合，将探索这些机制对环境压力耐受性的影响。本研究将解决植物表观基因组募集DNA修复机制的功能和适应价值等关键问题。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。