# Mechanisms of Base Excision DNA Repair

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $390,000

## Abstract

Abstract: DNA damage arises spontaneously from endogenous and exogenous sources and multiple DNA
repair pathways are required to identify and repair sites of damage. Failure to repair damage can result in cell
death or mutations. Somatic mutations accumulate as we age and result in a wide spectrum of diseases
including cancer. Our long-term goal is to elucidate the molecular mechanisms by which DNA repair enzymes
function and identify the key biophysical and biochemical principles that are important for successful DNA
repair. A fundamental understanding of DNA repair enzymes is immensely valuable as it provides a framework
for understanding the relationships between genotype and phenotype, exposure-induced mutagenesis risks,
and in rationally improving treatments that directly or indirectly cause genotoxic stress, such as cancer therapy.
This proposal will focus on repair of the most abundant forms of DNA damage both because of the clear
biological importance, and because these are excellent model DNA repair systems to elucidate basic principles
that may be applied broadly to understanding many DNA repair pathways. We will primarily focus on human
enzymes because of the opportunities to immediately translate experimental findings in the context of specific
diseases and treatments. We take an interdisciplinary approach to combine different types of structural and
biophysical information and to integrate information across multiple time and size scales. This work builds upon
our core strength in transient kinetics with rigorous structure/activity analysis. Although the focus of this project
is in uncovering the fundamental biological mechanisms for DNA repair, we will combine forces with a diverse
set of collaborators who bring unique perspective and training that will allow us to pursue translational and
clinical aspects of DNA repair that pertain to specific disease contexts.

## Key facts

- **NIH application ID:** 10818575
- **Project number:** 5R35GM149546-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Patrick J O'Brien
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818575

## Citation

> US National Institutes of Health, RePORTER application 10818575, Mechanisms of Base Excision DNA Repair (5R35GM149546-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10818575. Licensed CC0.

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