# Choreography of Eukaryotic DNA Replication

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2021 · $551,723

## Abstract

PROJECT SUMMARY
DNA replication is undeniably important for life and as a consequence, cells have evolved mechanisms to
monitor replication fidelity and to coordinate completion of replication with other cell cycle events. The
goal of this project is to understand how cells choreograph the duplication of their chromosomes, and how
defects in DNA replication may contribute to some disorders in humans. Chromosome replication in
eukaryotes is a process that involves the regulation of multiple initiation sites (origins) per chromosome
that vary in their initiation timing (not all origins fire at the same time in S phase) and efficiency (not all
origins fire in every cell cycle). Understanding how origin use is regulated is therefore critical for
understanding how genome integrity is maintained. This notion is underscored by genetic disorders with
links to replication defects: 1) Meier-Gorlin Syndrome with its point mutations in genes essential for origin
licensing; 2) the mouse chaos3 mutation in a gene encoding part of the replicative helicase that is associated
with breast cancer in mice; and 3) forms of replication fork errors that potentially contribute to human
segmental copy number variants and autoimmune disorders such as lupus erythematosus. Yeast is an ideal
model organism for studying DNA replication because of its small chromosomes, well defined origin
sequences, ease of altering chromosome structure, and exceptional systems for genetic and genomic
analysis. This project will address outstanding questions regarding why the choreography of chromosome
replication is so important in eukaryotes: why do origins initiate replication at different times, what
distinguishes origins in different temporal categories, what is the molecular basis for inefficient origins, and
how do defects in replication origin firing and/or fork progression lead to genome instability and
consequent disease states?

## Key facts

- **NIH application ID:** 10136629
- **Project number:** 5R35GM122497-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** BONITA J BREWER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $551,723
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136629

## Citation

> US National Institutes of Health, RePORTER application 10136629, Choreography of Eukaryotic DNA Replication (5R35GM122497-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136629. Licensed CC0.

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