# Cell Cycle Re-entry from quiescence

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $301,792

## Abstract

Project Summary/Abstract
Development, tissue renewal and long term survival of multi-cellular organisms is dependent upon the
persistence of stem cells that are quiescent, but retain the capacity to re-enter the cell cycle to self-renew, or to
produce progeny that can differentiate and re-populate the tissue. Deregulated release of these cells from the
quiescent state, or preventing them from entering quiescence, results in uncontrolled proliferation and cancer.
Conversely, loss of quiescent cells, or their failure to re-enter cell division, disrupts organ development and
prevents tissue regeneration and repair. Understanding the quiescent state and how cells control the
transitions in and out of this state is of fundamental importance. And yet, we know relatively little about it, due
to a lack of tools for identifying and studying quiescent cells in their natural setting. We propose to identify
genes that influence the entry, maintenance and recovery from the quiescent state in budding yeast cells. The
quiescent state of budding yeast shares many important features with that of higher cells and the cell cycle is
fundamentally conserved. As such, the strategies for arresting and maintaining this non-dividing quiescent
state are likely to be shared. Entry into quiescence requires a stable but reversible arrest in G1. We are
defining the mechanism of this G1 arrest and, as expected, we find striking parallels with the transition to
quiescence in higher cells. Using flow cytometry, we have shown that wild type yeast grown to stationary
phase differentiate into at least three cells types, only one of which bears the properties of quiescent cells. We
can track, quantify and purify these quiescent cells. We have observed considerable variation in the yield and
longevity of quiescent cells in lab and wild yeast strains. We are taking advantage of this natural variation and
new genomic approaches to identify polymorphisms in essential and non-essential genes that influence the
longevity of quiescent cells or regulate the entry into this state. It is our hope that discoveries made in budding
yeast will offer testable models for the regulation of these important pathways in metazoan cells.

## Key facts

- **NIH application ID:** 9965971
- **Project number:** 5R01GM120318-04
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** LINDA L. BREEDEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,792
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965971

## Citation

> US National Institutes of Health, RePORTER application 9965971, Cell Cycle Re-entry from quiescence (5R01GM120318-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965971. Licensed CC0.

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