This federal Project Grant award from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), provides $546,146 to Kent State University to conduct research on the structure, accessibility, and extension of telomeric overhangs - the single-stranded regions at the ends of chromosomes. The research aims to gain a mechanistic understanding of how the length, structure, and interactions of these telomeric overhangs with regulatory proteins impact their accessibility to enzymes like telomerase. Specific objectives include determining the impact of overhang length, regulatory proteins, and small molecules on the accessibility of the overhangs to telomerase, nucleases, and DNA damage response activators. The research will also investigate how relevant physiological factors affect telomerase-catalyzed telomere extension and the folding patterns of newly synthesized telomeres. The project period runs from Feb 1, 2025 to Jan 31, 2030 and leverages single-molecule fluorescence, cryo-electron microscopy, and computational modeling approaches to address these key questions.