# Mechanisms and Functions of ATR signaling

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2022 · $464,467

## Abstract

Project Summary
The long-term goal of the proposed research is to understand how cells preserve genome integrity.
Specifically, this application focuses on the ATR (ATM and rad3-related) signaling pathway. ATR functions at
the apex of a DNA damage and replication stress response pathway that is needed every cell division cycle to
promote the complete and accurate duplication of the genome. Many cancer cells are highly dependent on
ATR function for proliferation and viability because of elevated levels of oncogene-induced replication stress
and mutations in other genome maintenance pathways. Thus, ATR may be a useful drug target based on a
synthetic lethal approach. ATR inhibitors are currently in clinical trials in a variety of cancer settings. We
previously found that there are two independent ATR signaling complexes formed by TOPBP1 or ETAA1. In
this proposal we examine the functions of these alternative ATR complexes, explore how these proteins
activate ATR, and examine how ATR is regulated in response to different types of replication challenges. This
is a focused proposal aimed at understanding the most important and least understood aspects of ATR
function. Specific hypotheses and innovative concepts based on preliminary data are tested using advanced
biochemical and genetic approaches. In addition, the aims provide opportunities for unexpected discoveries
about the mechanisms that maintain the genome and when ATR pathway inhibitors may be useful in the
cancer clinic.

## Key facts

- **NIH application ID:** 10347345
- **Project number:** 5R01CA239161-04
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** David K Cortez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $464,467
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347345

## Citation

> US National Institutes of Health, RePORTER application 10347345, Mechanisms and Functions of ATR signaling (5R01CA239161-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10347345. Licensed CC0.

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