Mechanisms for the propagation of R-loop induced chromosomal fragments in the germline

Genetics, the study of heredity, aims to understand how genetic material is passed from one generation to the next. Reproduction of multicellular organisms requires formation of egg and sperm cells. This project will examine how these specialized cells are generated, focusing on how DNA breaks that occur during this process are managed. The outcomes will help to define rules important for the propagation of species. The project will include educational activities to improve literacy in genetics of young K-12 students from diverse backgrounds. The students will be introduced to basic concepts in genetics through interactions with university students and by applying play and creative exploration approaches. These activities will fulfill a need for STEM education during the summer for young student populations who would not otherwise be exposed to science, while providing undergraduate students with training on curriculum development. In addition, the project will provide research training opportunities for undergraduate and graduate students. Past research has shown that chromosome breaks in eggs can result from accumulation of structures involving long association between RNA and DNA. Broken chromosomes can either undergo double strand break repair or be capped with telomere sequences that block repair. This project will investigate how the latter mechanism stabilizes chromosome breaks induced by RNA-DNA hybrids and leads to their transmission into egg cells. Aim 1 will identify mechanisms by which chromosome repair is blocked, leading to addition of newly created telomeres to chromosome ends. Aim 2 will examine how the capping process is stimulated by the same events that lead to formation of chromosome breaks. The studies will be performed in the model organism Caenorhabditis elegans using cell biology and genetic techniques. The research is expected to provide crucial insights into fundamental biological and genetic processes required for the formation of eggs and sperm with intact and functional chromosomes. This project is jointly funded by the Genetic Mechanisms program in the Division of Molecular and Cellular Biosciences and the Established Program to Stimulate Competitive Research (EPSCoR). 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.