# Structural biology of telomerase and telomeres

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $218,535

## Abstract

Project Summary/Abstract
Telomeres, the physical ends of linear chromosomes, are composed of short repeating sequences (TTGGGG in
the G-strand for Tetrahymena thermophila and TTAGGG in human) of double-strand DNA with a single-strand
3′ overhang of the G-strand and, in humans, six proteins collectively called shelterin. Of these, TPP1–POT1
associate with the 3′ overhang, where POT1 binds the G-strand and TPP1 functions to recruit telomerase via
interaction with telomerase reverse transcriptase (TERT). The telomere DNA 3’-ends are replicated and
maintained by telomerase, for the G-strand and subsequently DNA polymerase α–primase (PolαPrim) in
complex with CTC1–STN1–TEN1 (CST), for the C-strand. In Tetrahymena, orthologous proteins p50 (TPP1),
Teb1 (POT1), and CST are constitutively associated with telomerase. Mutations that affect their activity or
regulation have profound effects on human health. Recent cryoEM structures and other studies on Tetrahymena
and human telomerase and these interacting partners set the stage for our goals to illuminate the detailed
mechanism and regulation of G-strand and C-strand synthesis at telomeres. Our focus will be on two broad
aspects of human and Tetrahymena telomerase and telomere structural biology: (A) telomerase mechanism,
assembly, and disease and (B) C-strand synthesis by CST–PolαPrim. Our research approach will primarily
involve complementary applications of cryoEM and NMR spectroscopy along with rigorous biochemistry and
molecular biology. Results on the two organisms will provide complementary information on shared structures
and mechanisms while also providing an evolutionary perspective for divergent organisms. Additionally, (C) we
will extend from single particle cryoEM to cryoET to visualize telomerase at telomeres in situ.

## Key facts

- **NIH application ID:** 11098255
- **Project number:** 3R35GM131901-06S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** JULI FEIGON
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $218,535
- **Award type:** 3
- **Project period:** 2019-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098255

## Citation

> US National Institutes of Health, RePORTER application 11098255, Structural biology of telomerase and telomeres (3R35GM131901-06S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11098255. Licensed CC0.

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