Molecular dissection of protein poly(ADP-ribosyl)ation in plant immunity and pathogen-induced DNA damage

植物的免疫反应是由广泛的过程共同代表的，这些过程已经进化到在病原体和害虫感染期间保护植物。在植物用来保护自己的各种反应中，此外，病原体针对使植物免疫系统失效的过程中，DNA的损伤——支撑所有生命的遗传密码——是植物和病原体相互作用的一个关键点。在目前的研究中，研究人员提出：植物如何在病原体感染期间保护和修复DNA损伤，以确保免疫系统继续发挥作用。该领域的先前研究表明，至少有一种类型的修复机制-聚（adp -核糖基）化（即PARylation） -在维持细胞存活和免疫信号传导中起关键作用。简而言之，这种机制具有检测和修复植物（宿主）DNA损伤的能力。作为病原体感染期间免疫所需的关键过程，研究人员将验证PARylation在植物免疫和病原体诱导的DNA损伤之间提供机制联系的假设。病原菌侵染后通过蛋白PARylation和基因组完整性调控植物免疫的分子和生化机制将被确定。这些研究产生的知识有望帮助设计更好的作物改良疾病控制策略。PARylation主要由聚（adp -核糖）聚合酶（PARP）介导，该酶将adp -核糖片段从NAD+转移到受体蛋白。这种修饰是可逆的，共价连接的聚（adp -核糖）可以通过聚（adp -核糖）糖水解酶（PARG）从受体蛋白上切割。由于在各种炎症和恶性疾病，特别是癌症化疗中具有深远的医学影响，PARylation在人类中已被广泛表征。然而，人们对PARylation在植物中的作用知之甚少。拟南芥parp和parg null突变体的生存能力和正常生长为研究包括植物免疫和DNA损伤修复在内的多种细胞过程中的蛋白质parp修饰提供了独特的机会。这项工作的结果将为理解DNA损伤和植物防御反应这两种基本监测机制如何错综复杂地相互联系和协调作用提供新的见解。本课题旨在揭示PARylation在植物免疫中的调控机制，确定PARylation调控的免疫基因和蛋白的靶点，阐明病原体诱导的DNA损伤机制及PARylation对其的保护作用。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。

Immune responses in plants is collectively represented by a wide range of processes that have evolved to protect plants during pathogen and pest infection. Among the various responses plants use to defend themselves, and moreover, processes that pathogens target to disable the plant immune system, damage to DNA – the genetic code that underpins all of life – is one key point of interaction between plants and pathogens. In the current study, the investigators ask: How do plants protect and repair damage to DNA during pathogen infection to ensure that the immune system continues to function. Previous research in this area suggests that at least 1 type of repair mechanism – poly(ADP-ribosyl)ation (i.e., PARylation) – plays a critical role in a maintenance of cell survival and immune signaling. In short, this mechanism has the ability to detect and repair damage to the plant (host) DNA. As a key process required for immunity during pathogen infection, the researchers will test the hypothesis that PARylation provides a mechanistic link between plant immunity and pathogen-induced DNA damage. The molecular and biochemical mechanisms underlying the regulation of plant immunity by protein PARylation and genome integrity after pathogen infection will be determined. Knowledge generated from these studies is expected to help design better disease control strategies for crop improvement.PARylation is primarily mediated by poly(ADP-ribose) polymerase (PARP), which transfers ADP-ribose moieties from NAD+ to acceptor proteins. This modification is reversible and the covalently attached poly(ADP-ribose) can be cleaved from acceptor proteins by poly(ADP-ribose) glycohydrolase (PARG). PARylation has been extensively characterized in humans due to its profound medical impacts in various inflammatory and malignant disorders and especially cancer chemotherapy. However, the function of PARylation in plants is poorly understood. The viability and normal growth of Arabidopsis parp and parg null mutants provide a unique opportunity to study protein PARylation in diverse cellular processes, including plant immunity and DNA damage repair at the whole organismal level. The results of the work will provide novel insights in understanding how the two fundamental surveillance mechanisms, DNA damage and plant defense responses, are intricately interconnected and function coordinately. This proposal aims to unravel the regulatory mechanisms of PARylation in plant immunity, identify the targets of PARylation-regulated immune genes and proteins, and elucidate the mechanism of pathogen-induced DNA damage and how it is protected by PARylation.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.