# Regulation of Telomere Maintenance in Fission Yeast

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $396,307

## Abstract

Project Summary/Abstract
Our laboratory is interested in understanding how eukaryotic cells ensure the maintenance of telomeres, the
natural ends of linear eukaryotic chromosomes. Evolutionarily conserved shelterin and CST (CTC1/Cdc13-
STN1-TEN1) complexes play essential roles in telomerase recruitment and protection of telomeres against DNA
repair and checkpoint factors. Stable maintenance of telomeres is critical to preserve genomic integrity and
prevent accumulation of undesired mutations that might lead to tumor formation. Regulation of telomere
structures and telomerase also affect cell proliferation and tissue maintenance in aging organisms. Therefore,
basic mechanistic studies investigating how telomere and DNA damage response proteins collaborate in proper
telomere maintenance should provide critical insights necessary to help devise more effective treatment
strategies against tumors or other age-related diseases. Our proposed research projects utilize fission yeast
Schizosaccharomyces pombe. Fission yeast telomeres serve as a good model for human telomeres, since
proteins involved in telomere maintenance are highly conserved between fission yeast and humans.
Studies from our lab and others have provided detailed insights how fission yeast shelterin and Stn1-Ten1
ensure stable maintenance of telomeres in fission yeast. Those include findings that (1) Tel1ATM/Rad3ATR_
dependent phosphorylation of the shelterin subunit Ccq1 on Thr93 promotes telomerase recruitment by
promoting interaction between Ccq1 and the telomerase subunit Est1, and (2) SUMOylation of another shelterin
subunit Tpz1ree, on Lys242 facilitates Stn1-Ten1 recruitment to telomeres and limits telomere extension.
Evolutionarily conserved "TEL patch" residues within Tpz1 have also been found to promote telomerase
activation and recruitment, further highlighting the well conserved nature of telomere regulation by fission yeast
and mammalian shelterin. Our analyses of temporal binding patterns for DNA polymerases, telomerase, shelterin
and Stn1 found that shelterin subunits Rap1 and Poz1 and the Stn1-Ten1 complex promote timely dissociation
of telomerase from telomeres by promoting recruitment of Pola to complete lagging strand synthesis at
telomeres. For the current grant application, our proposed experiments will (1) identify and characterize
underlying regulatory mechanism(s) that allow Ccq1 and Poz1 to promote Pola-dependent telomere protection
(Aim 1), (2) identify new interaction partners of Stn1-Ten1 complex and characterize their contributions to
recruitment/retention of Stn1-Ten1 complex at telomeres and non-telomeric sites (Aim 2), and (3) investigate
how regulation of TERRA vs. poly(A)+ TERRA expression modulates Stn1-Ten1-Pola recruitment at telomeres
(Aim 3).

## Key facts

- **NIH application ID:** 10519426
- **Project number:** 1R01GM143316-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Toru Nakamura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,307
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519426

## Citation

> US National Institutes of Health, RePORTER application 10519426, Regulation of Telomere Maintenance in Fission Yeast (1R01GM143316-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10519426. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*