Intellectual merit: Telomeres are specialized structures located at the ends of linear eukaryotic chromosomes. These structures consist of repetitive DNA sequences and a complex array of proteins that cap chromosome ends and protect chromosomes from deleterious rearrangements. The overall goal of this research is to investigate the mechanisms of the Cdc13-Stn1-Ten1 (CST) protein complex, which constitutes a critical and widely conserved component of telomeres. Despite a great deal of analysis, there are numerous gaps in the current understanding of how this complex is put together and how it protects telomere DNA. Preliminary studies uncovered two unexpected features of the CST complex: it is dimeric and contains more copies of Stn1 than the other subunits. Moreover, a second Cdc13-like protein (called Cdc13B) that regulates telomeres was identified in many Candida species. By analyzing the detailed interactions among the CST components and those between CST and telomeric DNA, this research will provide critical insights on how the cells maintain chromosome stability. In addition, by studying the functional overlap or diversification between Cdc13 and Cdc13B, this investigation will expand current understanding of the evolution of telomeres. The findings are also likely to influence telomere research in other organisms.
Broader impact: This project includes the training and development of underrepresented minority undergraduates at Hostos Community College (HCC), part of the City University of New York (CUNY). Motivated students will receive initial training at their home institution in a specially tailored laboratory course. They will then directly participate in the project during summer internships. Due to the well-established nature of the protocols for subsets of the experiments, the students will have realistic opportunities for making meaningful contributions to the project. The students' achievements will be showcased at HCC and other forums. Scientific reports authored by students will be published in the HCC on-line journal Hostos Journal of Student Research. They will also be presented at the Annual Biomedical Research Conference for Minority Students (ABRCMS). These activities should generate interest among peers at HCC and beyond, and help motivate and encourage these students to pursue careers in science. Moreover, while the project has a primary focus on telomere biology, the findings will also provide general insights on protein-nucleic acid interactions as well as on the co-evolution of proteins and their DNA-targets.
