# Molecular Mechanisms of Telomere Length Homeostasis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $393,963

## Abstract

Project Summary
The long-term goal of this proposal is to understand, in detail, the molecular mechanisms of
telomere length homeostasis through comprehensive biochemical, structural and functional
characterizations of the telomeric shelterin complex and its interaction with telomerase.
Telomeres ensure genome integrity by facilitating chromosome end replication through
telomerase and protect the chromosome ends from DNA repair and degradation activities.
Mutations in telomerase subunits or shelterin components have been linked to premature aging
and cancer. Shelterin complex and shelterin-telomerase interactions play essential roles in
regulating synthesis of telomeric DNA repeats and defining telomere lengths that support or
restrict cell proliferation. We will exploit the genetically amendable fission yeast model system
and employ a combination of biochemical, high-resolution structural and genetic tools to achieve
the following specific aims: 1. Elucidate the biochemical and structural basis of shelterin
assembly and its role in telomere length control; 2. Determine the mechanistic basis for
telomere switching from the telomerase non-extendible to extendible state; 3. Determine how
the activation of non-extendible telomeric state is coupled to telomerase recruitment.
Accomplishment of the proposed aims will provide new and significant mechanistic insights into
the structure-function relationship and the dynamics of the shelterin complex, and set up the
foundation for the development of new therapeutic approaches against diseases caused by
telomere dysfunction, such as premature aging.

## Key facts

- **NIH application ID:** 9983744
- **Project number:** 5R01GM098943-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Feng Qiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,963
- **Award type:** 5
- **Project period:** 2012-05-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983744

## Citation

> US National Institutes of Health, RePORTER application 9983744, Molecular Mechanisms of Telomere Length Homeostasis (5R01GM098943-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983744. Licensed CC0.

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