Mechanisms of Mitochondrial Deletions and Double-strand Break Repair

智力优势：真核细胞含有线粒体，这是一种为细胞产生能量的膜结合细胞器。与细胞核一样，线粒体也含有DNA基因组，其维持无误对细胞的正常功能至关重要。线粒体DNA大片段的缺失在许多类型的细胞中都是常见的突变。在许多物种中，这些突变随着年龄的增长而积累，并与代谢综合征有关。这种类型的缺失也通常在面包酵母的线粒体DNA中观察到。可用于酵母研究的分子工具使其成为线粒体生物学研究的有力模型。该项目的长期目标是了解导致线粒体缺失突变的基本细胞过程。研究的目的是了解参与这一过程的蛋白质及其活性，以及了解双链断裂在缺失突变产生中的作用。这项工作的完成将为线粒体DNA交易的广泛领域提供信息，包括复制、重组和修复。更广泛的影响：这项工作将对两所大学的生物科学本科生的教育产生积极的影响，因为这个项目是两所当地大学实验室之间的合作努力。罗切斯特大学的伊莱恩·希亚博士和纽约州立大学布罗克波特分校的雷伊·希亚博士有在实验室指导本科生的历史，在过去的两年半里，他们总共指导了20名本科生进行独立研究。酵母研究非常适合缺乏经验的本科生，使他们能够在夏季或学期中学习大量的技术和概念。将继续作出特别努力，通过与CSTEP/McNair和夏季REU项目的联系，从科学界代表性不足的群体中招募个人，或第一代大学生。项目负责人和联合负责人继续履行他们对科学教育的承诺，让纽约州立大学布罗克波特分校和罗切斯特大学的生物学本科生参与到这个项目中来。

Intellectual merit: Eukaryotic cells contain mitochondria, the membrane-bound organelles that produce energy for the cell. Like the nucleus of the cell, mitochondria contain DNA genomes, whose maintenance without error is essential to the normal function of cells. Deletions of large segments of the mitochondrial DNA are common mutations in many types of cells. In many species, these mutations accumulate with age and are associated with metabolic syndromes. Deletions of this type are also commonly observed in the mitochondrial DNA of baker's yeast. The molecular tools available for research in yeast have made it a powerful model for the study of mitochondrial biology. The long-term goal of this project is to understand the fundamental cellular processes that contribute to mitochondrial deletion mutations. Studies are directed at understanding the proteins involved in this process and their activities, as well as understanding the role of double-strand breaks in the generation of deletion mutations. Completion of this work will provide information on the broad area of mitochondrial DNA transactions, including replication, recombination and repair.Broader impacts: This work will have a positive impact on the education of undergraduates in the biological sciences at two institutions, as this project represents a collaborative effort between labs at two local universities. Dr. Elaine Sia, at the University of Rochester, and Dr. Rey Sia, at SUNY-Brockport have a history of undergraduate mentorship of undergraduates in the laboratory, with a combined record of advising 20 undergraduates in independent study in the past 2.5 years. Studies with yeast are well suited to undergraduates with little experience, allowing them to learn a large number of techniques and concepts in a summer or semester. Special effort will continue to be made to recruit individuals from groups underrepresented in science, or first generation college students via connections with CSTEP/McNair, and summer REU programs. The PI and co-PI continue to honor their commitment to scientific education with the involvement of undergraduate biology majors at SUNY Brockport and the University of Rochester in this project.