# Defining the mechanisms and consequences of noncanonical telomere functions

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $500,186

## Abstract

Abstract
The canonical functions attributed to telomeres in textbooks are to protect chromosome ends
from degradation and fusion, both of which are confirmed drivers of genome instability and
tumorigenesis. We have discovered two new and unforeseen roles for telomeres that are crucial
for safeguarding the genome.
First, we found that by interacting during meiotic prophase with the LINC complex (linker of
nucleo- and cyto-skeleton), which spans the nuclear envelope, telomeres promote the nuclear
envelope breakdown needed for spindle formation and the meiotic nuclear divisions.
Remarkably, centromeres perform this function analogously in mitotic cell cycles, and indeed
sporadic contacts between centromeres and LINC during meiotic prophase can rescue the loss
of telomere-LINC contacts, indicating a surprising instance of telomere-centromere
interchangeability. What features of telomeres and centromeres endow them with the capacity
to control nuclear envelope breakdown and therefore cell cycle progression? Here we propose a
series of experiments to answer this question.
Second, we found that by providing a nuclear microdomain conducive to centromere assembly,
telomeres rescue a surprising tendency of centromeres to become dismantled upon meiotic
onset by the very factors (the meiotic endonuclease Spo11 and the meiosis-specific cohesin
Rec8) that define meiosis. Indeed, we found that expression of Spo11 or Rec8 (which are
normally meiosis-specific) in proliferating cells induces centromere dismantlement and
chromosome missegregation. Here we propose to determine the mechanisms of Spo11- and
Rec8-mediated centromere dismantlement, how telomeres promote the reassembly of
dismantled centromeres, and whether these observations are relevant to the growing list of
human cancers that mis-express meiotic proteins.
These studies will open up new frontiers by defining at the molecular level unanticipated
features of two key lynchpins of chromosome stability, telomeres and centromeres.

## Key facts

- **NIH application ID:** 10419653
- **Project number:** 1R01GM145820-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Julia Promisel Cooper
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $500,186
- **Award type:** 1
- **Project period:** 2022-05-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419653

## Citation

> US National Institutes of Health, RePORTER application 10419653, Defining the mechanisms and consequences of noncanonical telomere functions (1R01GM145820-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10419653. Licensed CC0.

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