# Structure and Dynamics of Telomeres and Telomerase

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2024 · $553,579

## Abstract

Project Summary
Telomeres are essential structures located at the ends of linear chromosomes that protect genomic integrity
by preventing chromosomal fusion, degradation, and activation of DNA damage response pathways. The
telomerase reverse transcriptase maintains telomere length to compensate for telomere erosion by adding
short DNA repeat sequences to chromosome ends. In the absence of telomerase, telomeres progressively
shorten with each cell division due to the end-replication problem and nucleolytic processing. Critically short
telomeres ultimately induce cellular senescence or apoptosis. Dysregulation of telomere homeostasis has
been implicated in many human diseases, including cancer and rare genetic syndromes. Yet, the molecular
mechanisms underlying telomere/telomerase biology and the interplay between telomere dysfunction and
disease pathology are still not fully understood. With our previous NIGMS funding, we investigated
telomeres/telomerase from ciliates, yeasts, and vertebrates to uncover conserved structural features of
telomerase RNA, protein subunits, and telomere DNA. We used a combination of biochemical, structural,
computational, and novel single-molecule biophysical methods to study the function and dynamics of
telomerase and telomere DNA. Our results, together with the progress made in other laboratories, advanced
detailed mechanistic models for telomerase enzyme assembly, spatiotemporal regulation of telomerase
recruitment to telomeres, telomere chromatin remodeling by shelterin proteins, and coordinated
conformational changes within telomerase during its complex catalytic cycle. We are now uniquely positioned
to critically evaluate these models with our established state-of-the-art methodologies. The insights gained
from this research will provide a framework for the development of new therapeutic strategies and preventive
measures for telomere-related disorders. Funding from the MIRA will provide the necessary resources and
flexibility to pursue new avenues of mechanistic research within the rapidly developing field of telomere and
telomerase biology.

## Key facts

- **NIH application ID:** 10842861
- **Project number:** 1R35GM153235-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Michael D Stone
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $553,579
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842861

## Citation

> US National Institutes of Health, RePORTER application 10842861, Structure and Dynamics of Telomeres and Telomerase (1R35GM153235-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10842861. Licensed CC0.

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