# Analysis of the Replication Stress Response

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2022 · $424,732

## Abstract

Project Summary
Billions of base pairs of DNA must be replicated trillions of times during a human lifetime. Adding to the
difficulty, replication is challenged by stresses including DNA template lesions, difficult to replicate sequences,
and conflicts with transcription. Cells employ multiple repair and signaling responses to replication stress
depending on the type, persistence, and location of the problem. We have employed proteomic and genetic
approaches to understand how cells overcome replication stress. These analyses identified several new
replication stress response proteins including RADX. RADX binds single-stranded DNA and prevents
replication fork cleavage by endonucleases. We hypothesize that it regulates the processes of replication fork
reversal and fork protection through its single-stranded DNA binding activity. We will test this hypothesis and
more generally characterize mechanisms that regulate fork reversal and protection using biochemical and
genetic approaches. Since cancer cells have elevated levels of replication stress and many cancer
therapeutics work by interfering with DNA replication, these studies will also generate discoveries that may be
translated into the cancer clinic.

## Key facts

- **NIH application ID:** 10457828
- **Project number:** 5R01GM116616-08
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** David K Cortez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $424,732
- **Award type:** 5
- **Project period:** 2015-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457828

## Citation

> US National Institutes of Health, RePORTER application 10457828, Analysis of the Replication Stress Response (5R01GM116616-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10457828. Licensed CC0.

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