Plk1 in DNA Replication

Purdue University, West Lafayette IN

Investigators

Abstract

Intellectual Merit: DNA replication has to be coordinated with cell division to ensure it occurs once and only once per cell cycle to maintain genomic stability. However, which signaling pathway(s) or molecule(s) serve as a link between such cell division events and DNA replication remains unknown. Although involvement of Polo-like kinase 1 (Plk1), a regulator of many cell division events, has been implicated in DNA replication, no direct Plk1 substrates have yet been identified for this process. The research goal of this project is to understand how Plk1 regulates DNA replication. This will be accomplished by analyzing how Plk1-mediated phosphorylation of specific proteins involved in initiation of DNA replication regulates DNA replication. Although increasing evidence supports a role of Plk1 in DNA replication, the more significant issues are how Plk1 exerts its function on proteins implicated in DNA replication and the nature of the signals that couple Plk1 to these events. This research will bridge this knowledge gap. The extent to which different aspects of DNA replication are regulated by Plk1 activity toward its substrates will be determined by an array of molecular and cellular techniques. By focusing on the role of Plk1 in DNA replication, the project challenges the traditional view that Plk1 functions only on cell division events. Because DNA replication is a significant process that occurs in every organism and Polo kinase is highly conserved across species, the research will have a broader impact in understanding DNA replication in other organisms. Broader Impact: This project will be conducted primarily by students, making undergraduate and graduate education a major focus. Using experiments designed to address research problems as the core for training, significant integration of research and education will be accomplished. Collaborating with various undergraduate research programs at Purdue, three students will be trained during a typical 10-week module. Thus, at least 9 African American students from Jackson State University will be trained. A Problem-Based Learning (PBL) approach will be implemented to train students in the laboratory and to stimulate scientific interest. The use of problems to introduce concepts will also provide a natural mechanism to highlight the interconnections among disciplines. The education plan will also have an impact on career choices of undergraduate populations.