# Mechanisms of DNA Homology-directed Genome Repair and Tumor Suppression

> **NIH NIH R35** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $21,401

## Abstract

Project Summary
Genetic studies, first done in model eukaryotes and more recently in mammals, have revealed that
homology-directed DNA repair (HDR) plays a critical role in the elimination of DNA double-strand
breaks and in the preservation of stressed or injured DNA replication forks. HDR is reliant on the tumor
suppressors BRCA1-BARD1, BRCA2, and PALB2, mutations in which cause breast, ovarian, and other
cancers. Progress in understanding how these tumor suppressors help mediate HDR and how their
mutational inactivation impacts upon genome integrity has been hampered by the challenge of purifying
them for mechanistic studies. Our research team has overcome this challenge, which uniquely
positions us to decipher the mechanisms by which these tumor suppressors support HDR. In
conjunction with a growing research team in the NCI-designated Mays Cancer Center at the University
of Texas Health Science Center at San Antonio and with external collaborators who are leaders in
structural biology and single-molecule biophysics, we will dissect the underlying mechanisms of
different stages of HDR, to specifically furnish insights regarding the roles of the aforementioned tumor
suppressors therein. We will also pursue chemical screens and synthesis with the Cancer Prevention
and Research Institute of Texas (CPRIT)-supported Center for Innovative Drug Discovery to develop
inhibitors of HDR to use as a chemical biology tool and for preclinical studies. We are confident that our
holistic approach to deciphering HDR mechanisms will provide the foundation for developing targeted
cancer diagnostics and therapeutics.

## Key facts

- **NIH application ID:** 10690829
- **Project number:** 3R35CA241801-03S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Patrick Sung
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $21,401
- **Award type:** 3
- **Project period:** 2019-09-09 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690829

## Citation

> US National Institutes of Health, RePORTER application 10690829, Mechanisms of DNA Homology-directed Genome Repair and Tumor Suppression (3R35CA241801-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10690829. Licensed CC0.

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