CAREER: Meiotic double strand break repair on sex chromosomes

University Of Georgia Research Foundation Inc, Athens GA

Investigators

Abstract

DNA double strand breaks occur throughout the genome during meiosis and must be properly repaired to ensure overall genome stability. This process is challenging on sex chromosomes (i.e., X and Y) because there is limited sequence shared by the two chromosomes available for repair. A clear understanding of how double strand breaks are resolved on these chromosomes is important, as it may have a role in maintaining essential gene function on an otherwise degenerating Y chromosome. In addition, errors in the process have been linked to several disorders, including sterility and sex reversal. This project will identify how double strand breaks are localized and repaired on X and Y chromosomes. It will also provide extensive training in research, teaching, and mentoring to junior scientists at all levels. Local secondary education teachers will also be recruited to develop inquiry-based curricula focused on sex chromosome biology. Finally, this project will enable a program at University of Georgia that supports undergraduate attendance at the annual Southeastern Population, Ecology, and Evolutionary Genetics Conference. The overall goals of this project are to use the young sex chromosomes of the threespine stickleback fish to (a) understand how double strand break initiation and repair occurs, and (b) clarify how these processes influence the preservation of gene function on the Y chromosome. An array of comparative and functional genomics, gene editing and cytogenetics approaches will be employed to address the specific aims. Aim 1 will determine how double strand breaks are localized and whether breaks are associated with sex-chromosome-specific changes in chromatin features. Aim 2 will identify the preferential repair templates for double strand breaks across sex chromosomes. Aim 3 will determine whether genes subject to non-crossover gene conversion on sex chromosomes have essential functions. The results of this project will be broadly applicable across species, as meiotic recombination is highly conserved across the tree of life and utilizes the same proteins to regulate double strand break initiation and repair on sex chromosomes and autosomes alike. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.