# DNA–Protein Cross-Linking Sequencing for Genome-Wide Mapping of Abasic Sites at Single-Nucleotide Resolution

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2023 · $119,124

## Abstract

Project Summary
Endogenous metabolism and environmental exposure can result in a battery of DNA lesions. Failure to repair
these DNA lesions gives rise to genome instability and mutation accrual, which lead to accelerated aging, cancer,
and neurodegenerative diseases. Abasic site (AP site) is one of the most prevalent forms of DNA damage.
Although AP sites are known to be repaired by AP endonuclease in human cells, the dynamics of AP site
induction and repair across the genome and the cellular factors modulating these processes remain elusive.
In this application, we aim to explore how site-specific induction and repair of AP sites are affected by toxicant
exposure and epigenetic alterations. We propose three specific aims to achieve our objective: 1) we will develop
a DNA-protein cross-linking followed by next-generation sequencing (DPC-Seq) method for mapping, at single-
base resolution, AP sites in the human genome after toxicant exposure; 2) we will explore how the formation and
repair of AP sites are influenced by epigenetic state of chromatin; and 3) we will employ DPC-seq and whole-
genome mutation analysis to examine how AP sites contribute to mutational signatures observed in cancer
genomes. To accomplish this proposal and enable my transition to an independent academic career, I
assembled a mentoring committee with expertise in animal models, bioinformatics, mutagenesis, and toxicology.
The proposed research is built upon my research experience/skill sets, strong preliminary data, and the proposed
mentoring plan.
The outcome of the proposed research will establish a new method for mapping AP sites at single-base
resolution and provide important insights into the occurrence and repair of AP sites and how they are influenced
by toxicant exposure and genomic contexts. The proposed research will also reveal the roles of AP sites in
cancer etiology, which will ultimately lead to better strategies for the prevention and therapeutic interventions of
human cancer. Moreover, this proposal will fill gaps in my training and collect the data for my independent
publications and research grant applications, thereby enabling me to transition to become an independent
scientist in the field of environmental toxicology.

## Key facts

- **NIH application ID:** 10723069
- **Project number:** 1K99ES035446-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Feng Tang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $119,124
- **Award type:** 1
- **Project period:** 2023-08-11 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10723069

## Citation

> US National Institutes of Health, RePORTER application 10723069, DNA–Protein Cross-Linking Sequencing for Genome-Wide Mapping of Abasic Sites at Single-Nucleotide Resolution (1K99ES035446-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10723069. Licensed CC0.

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