# Molecular Mechanisms of Telemere Length Homeostasis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $246,978

## Abstract

Project Summary
Telomeres ensure genome integrity by facilitating chromosome end replication through
telomerase, the activity of which enables cellular proliferation. Uncontrolled proliferation as may
occur in cancer cells requires hyper-activation of telomere-extension activity. Conversely, lack of
telomere extension results in degenerative disorders or premature aging. Critical to telomere
structure and function, the conserved multifunctional shelterin complex associates with
telomeres to coordinate multiple telomere activities. The long-term objective of our NIGMS
MIRA research program is to determine, at the atomic resolution, molecular mechanisms of
telomere length homeostasis through comprehensive biochemical, structural, and functional
characterizations of the telomeric shelterin complex, shelterin-telomerase interactions, and
telomerase biogenesis. Mutations in telomerase subunits or shelterin components have been
increasingly linked to cancer and premature aging. 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. Our recent efforts have achieved the
conceptual advancement on the role of shelterin bridge, rather than individual shelterin
component per se, in regulating telomere length and the landmark determination of the atomic
views of shelterin bridge assembly process by x-ray crystallography. Our accumulated
expertise and prior success position us to deepen our investigations. In the next five years, we
aim to address the following three fundamental questions in the field: 1) Elucidate the
biochemical and structural basis of the assembly of whole fission yeast shelterin complex and
its role in telomere length control; 2) Determine the mechanistic basis of shelterin disassembly;
3) Determine the structural basis of telomerase RNA folding quality control mechanism by Pof8
complex. Accomplishment of the proposed studies will provide new and significant mechanistic
insights into the maintenance of our chromosome ends 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:** 11037462
- **Project number:** 3R35GM149572-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Feng Qiao
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,978
- **Award type:** 3
- **Project period:** 2023-04-13 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037462

## Citation

> US National Institutes of Health, RePORTER application 11037462, Molecular Mechanisms of Telemere Length Homeostasis (3R35GM149572-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11037462. Licensed CC0.

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