# Cross-Validation of Genome Integrity Assays in Primary Human Cells

> **NIH NIH U01** · UNIVERSITY OF MINNESOTA · 2020 · $154,000

## Abstract

PI: Laura Niedernhofer
Measuring nucleotide excision repair in human populations
Nucleotide excision repair (NER) is a DNA repair mechanism that recognizes and removes bulky, helix-
distorting lesions from the nuclear genome. Key substrates for NER are lesions induced by ultraviolet (UV)
radiation upon environmental exposure to sunlight and a subset of oxidative DNA lesions produced
endogenously implicated in neurodegeneration. Subtle defects in NER, due to, for example, polymorphisms in
NER genes, might modestly but significantly impact one’s risk of skin cancer. The greatest barrier to identifying
those at risk is the lack of an assay to measure NER that is rapid, inexpensive and applicable to samples
safely and easily collected from patients. Historically, UDS measurement required the use of radioactively
labeled nucleosides and/or specialized equipment. We developed a method to measure NER that employs the
thymidine analog 5-ethynyl-2'-deoxyuridine and Click-iT chemistry for fluorescent detection of UDS by flow
cytometry. This project aims to correct gaps in knowledge about variability and heritability of DNA repair
capacity through optimization of our functional assay and proof-of concept pilot human studies. Our assay is
being applied to existing cohorts of patients seen at the University of Miami Skin Cancer Clinics, the NIH
Undiagnosed Diseases Program (UDP) and the Amish Longevity Study to interrogate associations between
NER capacity and high risk of skin cancer, early onset neurodegeneration, and within family pedigrees,
respectively. The assay could have a significant impact on how risk of squamous cell or basal cell carcinoma of
the skin, melanoma, lung or head and neck cancer, neurodegeneration, and resistance to cancer
chemotherapy is identified and managed.

## Key facts

- **NIH application ID:** 10140601
- **Project number:** 3U01ES029603-03S3
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** LAURA Jane NIEDERNHOFER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $154,000
- **Award type:** 3
- **Project period:** 2018-09-21 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140601

## Citation

> US National Institutes of Health, RePORTER application 10140601, Cross-Validation of Genome Integrity Assays in Primary Human Cells (3U01ES029603-03S3). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10140601. Licensed CC0.

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