# THE ROLE OF TELOMERASE REGULATORS IN TELOMERE MAINTENANCE AND GENOMIC INSTABILITY

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $8,443

## Abstract

Project Summary
 Mammalian chromosome ends or telomeres are tightly regulated by the telomerase that mediates
telomere elongation and telomere-binding proteins that cap and protect telomere ends. Telomere DNA
normally adopts a closed conformation, capped and protected by a multitude of telomere-binding proteins, to
prevent DNA damage and genome instability. Telomeres become open and linear during DNA replication to
enable telomerase access for telomere elongation. Exposed and critically short telomeres, as a result of
mutations in telomerase and telomere regulators, also become open and susceptible to damage and genome
instability, ultimately leading to cancer. Mutations in telomere-binding proteins and the TERT promoter have
been identified in a number of cancers. Most cancer cells have up-regulated telomerase expression and
activities, and cancer cells appear highly sensitive to perturbations in telomerase activities and telomere
capping, making the telomerase attractive for therapeutic targeting. A comprehensive study of telomerase
regulators therefore should greatly facilitate our understanding of telomerase dysregulation in cancer and the
discovery of new drug targets. We have developed an arrayed whole-genome protein interaction network
screening strategy based on the Bi-molecular Fluorescence Protein Complementation (BiFC) assay. A pilot
TERT BiFC screen identified several proteins as key components of the telomerase complex, including a
protein we named TARP1 that has never been characterized before. We propose here to screen genome wide
for cell cycle-dependent regulators of the telomerase, and to examine the mechanisms and function of the
TARP1-telomerase complex. We will use inducible TARP1 knockout cells generated by CRISPR/Cas9 as well
as mouse xenograft models for these studies. Our work will have important implications in devising effective
treatment strategies for cancers that result from telomere dysfunction induced genome instability.

## Key facts

- **NIH application ID:** 9840457
- **Project number:** 5R01CA211653-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Alison A Bertuch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $8,443
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840457

## Citation

> US National Institutes of Health, RePORTER application 9840457, THE ROLE OF TELOMERASE REGULATORS IN TELOMERE MAINTENANCE AND GENOMIC INSTABILITY (5R01CA211653-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9840457. Licensed CC0.

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