Intellectual Merit. The overall goal of this project is to increase understanding of the mechanisms that govern genetic recombination in mammalian chromosomes. The term "genetic recombination" refers to a process in which segments of DNA are exchanged between two chromosomal regions. Recombination plays an important role in the evolution of genomes, contributes to genetic diversity, and provides a means for repair of DNA damage that occurs on a daily basis. Although recombination is generally beneficial, it may be viewed as a double-edged sword. While recombination helps to maintain the integrity of chromosomes, it is critical that mechanisms exist to assure that exchanges are allowed to occur only between appropriate chromosomal regions so that potentially deleterious genetic rearrangements are avoided. For the most part, recombination must be restricted to DNA segments that share a high degree of identity in order for deleterious exchanges to be precluded, but little is known about how cells regulate recombination. In this research project, a novel set of engineered DNA molecules will be inserted into chromosomes in mouse cells, and these molecules will allow recombination events to be monitored. The various DNA molecules are designed to test the cell's ability to carry out recombination between DNA segments sharing different degrees of identity. These studies will illuminate the rules normally employed to decide which DNA segments can engage in recombination, and which DNA segments are excluded from such exchanges. Also to be investigated is the question of whether certain forms of DNA damage might alter the rules of recombination. The roles played by certain proteins in the regulation of recombination will also be explored. This project will provide a clearer picture of how recombination can both shape and maintain the mammalian genome.
Broader Impacts. This project will make substantive contributions to general science education and practical scientific training. The research will be conducted in a laboratory that is located in a large undergraduate Department of Biological Sciences that is responsible for educating more than 1600 undergraduate majors. The laboratory in which this work will be done has a history of offering research experiences for undergraduates and this project will continue this history. It is noteworthy that the Department of Biological Sciences at the University of South Carolina has a very diverse student body, and so this project will afford an important opportunity for providing research experiences for traditionally underrepresented groups. In the past, this project's Principal Investigator (PI) has served as mentor to African American and women undergraduates, and these research experiences have encouraged several individuals to choose careers in science. The PI has also served as mentor to numerous masters and doctoral degree students from the U.S. and abroad and this research project will continue this important training of new scientists. Several Historically Black Colleges and Universities are within proximity to the University of South Carolina. The PI will visit these institutions to present scientific seminars reporting the results of the funded work and will use such engagements to talk with students about graduate school opportunities and the possibility of pursuing a career in science. The PI will also visit with students in grades K-12 to discuss career opportunities in science, research results, and general issues related to science. In addition to potentially encouraging careers in science, these latter outreach activities may serve to enhance the scientific literacy of the public.
