Intellectual merit. Cell division is a fundamental feature of all life and involves the precise transmission of genetic information from mother to daughter cells. Each cell division cycle is therefore executed as a tightly regulated, stepwise program. Ubiquitin and SUMO, two small proteins that are attached to other cellular proteins to signal their destruction, control important aspects of the cell division program in eukaryotic cells. Ubiquitin's essential role in the timely destruction of key cell cycle regulators is well documented, but the role of SUMO is less well understood. Research in the laboratory of the investigator has led to an important discovery that defines a novel role for SUMO in protein ubiquitination. Briefly, degradation of several nuclear proteins, including some that are involved in DNA repair and transcriptional regulation, are preceded by modification with SUMO. These sumoylated proteins are then recognized by SUMO-targeted ubiquitin ligases (STUbLs), which mediate their ubiquitination. Cells that lack specific STUbLs accumulate high levels of SUMO conjugates, chromosomal rearrangements, and become hypersensitive to DNA damage. This project now aims to elucidate the functional roles of SUMO-dependent protein degradation in the transmission and maintenance of genetic information. Briefly, the cellular pathways, targets, and interactions of STUbL proteins will be identified. Since STUbLs are conserved, this research will provide novel insights into our general understanding how genome integrity is maintained during the cell cycle, from yeast to humans.
Broader impacts. The investigator will continue to foster the involvement of a diverse group of students in the scientific discovery process by providing hands-on research opportunities in the teaching and research laboratory. For example, the investigator has developed and will involve students in the Genetic Model Systems Lab, a laboratory course that provides a real-life research experience to teach students of all levels and backgrounds about the powerful applications of genetic model systems in research. Additionally, outreach activities are planned as an integral part of the investigator's research. The lab will continue to host high-school and undergraduate student researchers from underrepresented backgrounds and will invites research collaborations with faculty from local colleges, universities, and high schools. Results of this research will be presented at scientific meetings and will be available through open-access research publications and a laboratory Web site. In coordination with the William and Mary Development Office, the laboratory will also participate in a program to invite visitors to the lab, including government officials, journalists, and other groups, to promote public understanding of our research.
