The long-term goal of this project is to elucidate the molecular mechanism responsible for the formation of the meiotic chromosome architecture and to examine the role chromosome organization plays in safeguarding genomic integrity. Mitosis and meiosis both require higher-order chromosome organization, which is achieved by the action of a conserved and essential protein complex called condensin. In mitosis, however, there is only one genetic division, that in which paired sister chromatids separate. In contrast, in meiosis two divisions occur. In the first, homologous chromosomes pair, recombine, and then separate; only in the second do the sister chromatids separate. Genetic studies of baker's yeast (Saccharomyces cerevisiae) have confirmed that condensin plays a role in condensation and segregation of meiotic chromosomes. The proposed research is focused on the in vivo cellular and biochemical activities of condensin in meiosis. Three complementary approaches will be employed: (1) A novel three-dimensional chromosome-tracking system will be developed for study of condensin function in chromosome organization and rearrangement at the point of their occurrence in live cells. (2) Genomic and proteomic techniques will be used to identify factors that interact with condensin. Their interaction with condensin will be characterized in the context of DNA topological changes and chromosome segregation. (3) An inducible DNA double-strand break will be created on the chromosome during meiosis so that the role of condensin in repair of the break can be examined.
This project involves both undergraduate and graduate students at Florida State University. The feasibility of projects using yeast genetics makes them particularly appropriate and attractive to undergraduate students, including minority students, who participate in a faculty-directed independent study program. This project will therefore enhance the education of undergraduate and graduate students as well as contribute to the advancement of chromosome research.
The goal of this project was to determine the role of condensin during meiotic recombination and chromosome segregation. We developed a novel chromosome-tracking tool in live cells and found that condensin plays two distinctive roles in suppressing meiotic recombination and promoting chromosome break repair. This project produced six peer-reviewed publications, most of which appeared in high-quality journals. Our work has provided insights into the genetic mechanism by which condensin and its related protein complex cohesin regulate chromosome dynamics and therefore ensure genomic integrity during cell division. A new direction of research has been initiated to determine the cohesin and condensin activities that are required for gene regulation during meiotic differentiation. This project trained four graduate students, 10 undergraduate students, two research technicians, and one postdoctoral researcher. Two graduate students, both are females, have received M.S. degrees from the Florida State University. Six undergraduate students, including one African American and two Hispanic students, have received B.S. degrees and graduated from the Florida State University. All former graduate students and two undergraduate students shared authorships in our publications. Research materials generated from this project have been incorporated into the curriculum of the Experimental Biology course – Yeast Genetics (BSC3402L) that the PI teaches at Florida State University. This federal support contributed to the education of our future workforce, including underrepresented and minority students.
