CAREER: Interactions Between Error-Prone and Error-Free DNA Double-Strand Break Repair Pathways in Drosophila Melanogaster

精确和可控的DNA双链断裂修复对细胞存活和基因组完整性至关重要。双链断裂可以通过许多准确和不准确的机制来修复。虽然精确的修复途径已经被广泛研究，但容易出错的双链断裂修复在机制水平上并没有很好地表征。本CAREER项目将阐明易出错断裂修复的遗传要求，并表征多细胞真核生物黑腹果蝇中各种双链断裂修复途径之间的动态相互作用。为了实现这些目标，研究生和本科生团队将利用报告系统来测量修复途径的相对使用，以研究发育和组织特异性线索如何影响修复途径的选择。他们将使用基于web的wiki来促进团队内部的有效沟通，并与更大的科学社区分享想法和协议。此外，这项研究将作为一门新的研讨会课程的基础，该课程将让学生对该领域的主要文献文章进行批判性分析。这个项目将进一步加深我们对分子生物学中一个关键问题的理解——在不断变化的多细胞环境中，各种DNA修复途径如何协调以确保基因组的稳定性。此外，它将深入了解容易出错的DNA修复途径促进遗传多样性的机制。在进行研究的同时，学生将参加指导研讨会和外展活动，旨在培养成功研究事业所需的技能。这些经历将鼓励他们在培训的早期阶段就掌握自己的研究和职业道路。因此，该项目应对保留面向研究的科学领域的学生，特别是那些来自传统上代表性不足群体的学生产生广泛影响。

Precise and controlled repair of DNA double-strand breaks is crucial for cell survival and genomic integrity. Double-strand breaks can be repaired by a number of both accurate and inaccurate mechanisms. Although accurate repair pathways have been extensively studied, error-prone double-strand break repair is not well characterized at the mechanistic level. This CAREER project will elucidate the genetic requirements for error-prone break repair and characterize the dynamic interactions between various double-strand break repair pathways in the multicellular eukaryote Drosophila melanogaster. To accomplish these objectives, teams of graduate and undergraduate students will utilize reporter systems that measure the relative use of repair pathways to study how developmental and tissue-specific cues affect repair pathway choice. They will employ web-based wikis to promote effective communication within the teams and to share ideas and protocols with the larger scientific community. In addition, the research will serve as the basis for a new seminar course that engages students in critical analysis of primary literature articles within the field.This project will further our understanding of a crucial question in molecular biology-how various DNA repair pathways are coordinated to ensure genomic stability in a constantly changing multicellular environment. In addition, it will provide insight into the mechanisms by which error-prone DNA repair pathways can promote genetic diversity. While conducting research, students will participate in mentoring workshops and outreach activities designed to develop skills required for successful research careers. These experiences will encourage them to take ownership of their research and career paths at an early stage in their training. The project should therefore have a broad impact on the retention of students in research-oriented scientific fields, particularly those students from traditionally underrepresented groups.