# Replication Licensing and the Cell Cycle

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $322,055

## Abstract

SUMMARY
Precise duplication of the entire human genome requires that many thousands of chromosomal initiation sites,
known as DNA replication origins, are utilized exactly once per cell cycle. Origin licensing is accomplished
through the DNA loading of precursor helicase complexes, and they are loaded exclusively during the G1
phase of the cell cycle. Licensing too few origins results in incomplete replication, and licensing origins that
have already been replicated results in re-replication. Both situations are sources of genome instability that can
lead to developmental defects, degeneration, or mutagenesis. Our goal is to understand how the origin
licensing process is achieved and how it is organized to ensure appropriate cell proliferation and genome
stability. Here, we propose to interrogate licensing control during early differentiation, explore the molecular
mechanism of an essential but mysterious licensing factor, and identify the mechanisms and pathways that
regulate origin licensing during cell cycle exit. We have designed innovative new tools and assays to quantify
and manipulate origin licensing in different human cell lines. We seek answers to questions such as the
following: 1) How is licensing coordinated to ensure genome stability over the course of profound G1 changes
that occur during differentiation? 2) How does the Cdt1 licensing factor function and how is it controlled? 3)
How is licensing blocked during the establishment and maintenance of cell cycle quiescence? Success in
answering these questions will shed light on an essential biological process that is fundamental to organismal
development and homeostasis. Moreover, we will investigate DNA replication and cell cycle control in cellular
settings that have not yet been explored in anticipation of revealing entirely new aspects of cell proliferation
control.

## Key facts

- **NIH application ID:** 9900791
- **Project number:** 5R01GM083024-09
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jeanette Gowen Cook
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $322,055
- **Award type:** 5
- **Project period:** 2009-01-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900791

## Citation

> US National Institutes of Health, RePORTER application 9900791, Replication Licensing and the Cell Cycle (5R01GM083024-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900791. Licensed CC0.

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