# Single-molecule Analysis of the DNA Damage Response in Living Cells

> **NIH NIH DP2** · MICHIGAN STATE UNIVERSITY · 2020 · $2,137,302

## Abstract

Project Abstract
DNA stores the heritable genetic information in human cells; however, DNA is constantly exposed
to endogenous and exogenous insults that can cause damage, threatening genomic integrity. To
counteract this damage, human cells have evolved a sophisticated machinery to detect DNA
damage, the DNA damage response. The DNA damage response facilitates engagement of
several pathways that can repair DNA abnormalities ranging from simple base-mismatches to
highly cytotoxic double-strand breaks. Defects in either DNA repair or DNA damage response
proteins underlie a wide range of human diseases, including neurological disorders,
immunodeficiency, infertility, and cancer. Therefore, understanding the molecular mechanisms of
DNA damage repair is highly significant for human health and could lead to new therapeutic
strategies to treat these diseases. DNA repair is carried out by a variety of enzymes, including
nucleases, ligases, recombinases, and other DNA modifying enzymes. Since these enzymatic
activities have evolved to alter their DNA substrate, they are inherently mutagenic. It is therefore
imperative that the activation of DNA repair proteins is tightly controlled and locally restricted to
the site of the DNA lesion. The goal of this project is to develop and implement live cell single-
molecule approaches to analyze how the DNA damage response senses genome alterations and
activates the appropriate pathway to repair the lesion. We will use these methods to build a
comprehensive, quantitative, mechanistic model of DNA repair in human cells. Importantly, a
quantitative understanding of DNA damage response could lead to new therapeutic approaches
to specifically reinforce or interfere with DNA repair in a wide range of human diseases.

## Key facts

- **NIH application ID:** 9999211
- **Project number:** 1DP2GM142307-01
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Jens Christopher Schmidt
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,137,302
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999211

## Citation

> US National Institutes of Health, RePORTER application 9999211, Single-molecule Analysis of the DNA Damage Response in Living Cells (1DP2GM142307-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999211. Licensed CC0.

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