# Determining the Function of HMCES in DNA Replication and Repair

> **NIH NIH F30** · VANDERBILT UNIVERSITY · 2020 · $50,520

## Abstract

Project Summary/Abstract
 Accurate and timely DNA replication is critical for maintaining genomic integrity. Replication forks
frequently encounter obstacles such as DNA lesions caused by environmental and endogenous genotoxic
agents, conflicts with transcriptional machinery, and unusual DNA structures that block the replicative DNA
polymerases leading to fork stalling. There are a large number of proteins that facilitate the resolution of stalled
forks. Recently, our lab identified 5-hydroxymethylcytosine binding ES cell-specific (HMCES), or C3orf37, as a
protein enriched at replication forks. HMCES contains one SOS Response Associated Protein (SRAP) domain
that is evolutionarily conserved through bacteria. A comparative genomics study found that the bacterial
HMCES gene is close to SOS operons in bacteria suggesting a function in responding to DNA damage.
However, to date, there have not been any functional studies of HMCES. Our preliminary data shows that
HMCES-deficient human cells have slow replication kinetics, increased sensitivity to genotoxic agents, and a
mutator phenotype. HMCES is recruited to replication forks and UV-damaged chromatin. HMCES binds DNA
and interacts directly with components of the replisome. To determine the function of HMCES in genome
maintenance, I will define how HMCES binds DNA and HMCES localization to replication forks and UV
damaged chromatin using mutagenesis, biochemical, and structural approaches. I will use genetic approaches
to test whether HMCES directly acts at replication forks to facilitate accurate completion of DNA synthesis.

## Key facts

- **NIH application ID:** 9849762
- **Project number:** 5F30CA228242-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Petria Thompson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849762

## Citation

> US National Institutes of Health, RePORTER application 9849762, Determining the Function of HMCES in DNA Replication and Repair (5F30CA228242-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849762. Licensed CC0.

---

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