# Functions of SRAP domain proteins in DNA metabolism

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $487,662

## Abstract

PROJECT SUMMARY
Thousands of abasic sites form daily in each of our cells. Many types of environmental toxins that cause
alkylation or oxidation of DNA bases to form N7-guanine adducts and 8-oxoguanine induce abasic sites.
For example, N-nitrosamines that are found in foods, detergents, solvents, plastics, and agricultural
chemicals as well as chemicals like carbon tetracholoride, potassium bromate, and chloroform that induce
oxidative stress all increase the frequency of abasic sites in DNA. Failures in managing this ubiquitous
form of DNA damage can cause a variety of diseases including cancer. The known mechanisms of repair
require an intact DNA duplex; however, abasic sites form more readily in single-stranded DNA where they
are impediments to replicative polymerases. We utilized unbiased proteomic and genetic approaches to
understand how replication forks deal with challenges to genotoxic stresses with the premise that
uncharacterized proteins identified in both approaches would be strong candidates for new DNA damage
response proteins. Both the proteomic and genetic screens identified HMCES (hydroxyl-methyl cytosine
embryonic cell specific) as a candidate genome maintenance protein functioning at replication forks.
HMCES was reported to bind and remove 5-hydroxymethyl cytosine from DNA and thereby regulate gene
expression. Our preliminary data suggests that HMCES independently functions as a replication-
associated DNA repair protein. HMCES contains an evolutionarily ancient domain (SRAP). We
hypothesize that SRAP proteins provide a mechanism to repair or tolerate DNA damage during DNA
replication. This proposal will utilize biochemical, genetic, and structural approaches in human, yeast, and
bacterial systems to determine how SRAP proteins maintain genome stability. Completing these studies
will generate paradigm setting discoveries within the fields of environmental toxicology, DNA repair, DNA
replication, epigenetic control, and enzymology.

## Key facts

- **NIH application ID:** 10077211
- **Project number:** 5R01ES030575-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** David K Cortez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $487,662
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077211

## Citation

> US National Institutes of Health, RePORTER application 10077211, Functions of SRAP domain proteins in DNA metabolism (5R01ES030575-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10077211. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*