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

DNA双链断裂的精确和受控修复对于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精确和不精确的机制来修复。 虽然准确的修复途径已被广泛研究，易错的双链断裂修复没有很好地表征在机制水平。 这个CAREER项目将阐明易错断裂修复的遗传要求，并描述多细胞真核生物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。 他们将使用基于网络的维基来促进团队内部的有效沟通，并与更大的科学界分享想法和协议。 此外，这项研究将作为一个新的研讨会课程，从事学生在该领域的主要文献文章的批判性分析的基础。这个项目将进一步加深我们对分子生物学中的一个关键问题的理解-如何协调各种DNA修复途径，以确保在不断变化的多细胞环境中的基因组稳定性。 此外，它将提供深入了解易错DNA修复途径可以促进遗传多样性的机制。 在进行研究的同时，学生将参加旨在培养成功的研究职业所需技能的辅导研讨会和推广活动。 这些经验将鼓励他们在培训的早期阶段掌握自己的研究和职业道路。 因此，该项目应能广泛影响学生留在面向研究的科学领域，特别是那些来自传统上代表性不足群体的学生。

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.