# Telomere structure and function in Arabidopsis

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2021 · $378,750

## Abstract

Project Summary:
 Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism. Environmental assaults can
dramatically elevate ROS, overwhelming the defenses of cellular antioxidants, and triggering damage to essential
macromolecules particularly DNA. Oxidative damage is linked to numerous disease states, but despite much
research, fundamental questions remain on how cells avert the detrimental impacts of ROS. Mounting evidence
implicates telomere proteins in functions beyond the chromosome terminus. Both Protection of Telomeres 1 (POT1)
and the telomerase catalytic subunit TERT traffic in and out of the nucleus and are implicated in various aspects
of the response to oxidative damage in mammalian cells. However, unmasking potential non-telomeric functions
is problematic because of their critical roles in telomere maintenance and stability. In this renewal application, the
model eukaryote Arabidopsis thaliana is employed to study how telomere-associated proteins (TAPs) respond to
and mitigate oxidative stress. Arabidopsis encodes two highly divergent POT1 paralogs, AtPOT1a and AtPOT1b,
which exhibit separation-of-function with respect to canonical telomere biology, and hence present a unique
opportunity to elucidate the full complement of POT1 functions. The proposal builds on additional preliminary
showing that AtPOT1b accumulates in the cytoplasm, and loss of AtPOT1b significantly elevates ROS and
activates numerous cellular defenses against oxidative stress. AtTERT carries a mitochondrial localization signal,
suggesting that it too may regulate the response to ROS. The central hypothesis of this proposal is that the TAPs,
AtPOT1a, AtPOT1b and AtTERT, serve important roles in the cellular defense against oxidative damage. This
hypothesis will be examined through two Specific Aims. For Aim 1, the breadth of POT1 functions in promoting
genome integrity will be assessed by testing how POT1a and POT1b regulate oxidative damage in telomeric and
non-telomeric DNA, and how POT1b cooperates with POT1a and TERT to avert genome destabilization. The role of
ATR signaling in reproductive progenitor cells will be examined in pot1b mutants. Finally, the evolutionary origin of
stress response functions in POT1 proteins will be explored. In Aim 2, three complementary strategies will probe the
molecular mechanism and interaction partners of TAPs in non-telomeric pathways. These include monitoring the
subcellular trafficking of TAPs in response to stress, quantitative mass spec to identify protein binding partners and
stress-induced post-translational modifications, and a novel suppressor screen to explore the genetic pathway that
enables POT1b and TERT to promote plant development. These studies will increase understanding of the cross-
talk between TAPs and the stress response, open new horizons for exploring the non-canonical functions of POT1,
and provide a roadmap to explore rare splice variants of human POT1 that cannot associate with telomer...

## Key facts

- **NIH application ID:** 10236539
- **Project number:** 5R01GM065383-18
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Dorothy Shippen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,750
- **Award type:** 5
- **Project period:** 2002-05-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236539

## Citation

> US National Institutes of Health, RePORTER application 10236539, Telomere structure and function in Arabidopsis (5R01GM065383-18). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10236539. Licensed CC0.

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