# Developmental control of replication initiation and genome stability

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2024 · $427,618

## Abstract

Project Summary
 Every cell division requires the faithful duplication of genetic material from
mother cell to daughter cell. Defects in the proper execution of the DNA
replication program can directly result in the genome instability that is a hallmark
of nearly all cancer cells. To ensure genome stability, the machinery responsible
for DNA replication must be highly regulated. There must be enough flexibility
built into the DNA replication program, however, to accommodate the dramatic
changes in cell cycle and S phase progression that occur during the development
of an organism. Understanding this regulation is imperative to determine how
genome stability is maintained during development.
 We utilize the powerful developmental systems available in Drosophila to
identify key regulators of the DNA replication program, with the ultimate goal of
delineating the molecular underpinnings responsible for regulating genome
duplication and stability during development. Our main focus is understanding
how replication initiation is regulated to ensure genome stability. We have
defined three key projects where the strength of our system positions us to make
key insights. These include: 1) understanding the functional relationship between
nuclear pore proteins and the Origin Recognition Complex (ORC). 2) Defining the
key targets and molecular mechanisms Rif1 uses to influence replication initiation.
3) Identifying and characterizing posttranslational modifications of ORC that
affect replication initiation.

## Key facts

- **NIH application ID:** 10764038
- **Project number:** 2R35GM128650-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Jared Nordman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,618
- **Award type:** 2
- **Project period:** 2018-09-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764038

## Citation

> US National Institutes of Health, RePORTER application 10764038, Developmental control of replication initiation and genome stability (2R35GM128650-06). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10764038. Licensed CC0.

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