# Mechanisms of DNA damage processing and the initiation of Nucleotide Excision Repair

> **NIH NIH R15** · BAYLOR UNIVERSITY · 2022 · $377,493

## Abstract

Project Summary:
Mechanisms of DNA damage processing and the initiation of Nucleotide Excision Repair
The goal of this research is to determine the structural mechanism of nucleotide excision repair
(NER) initiation. NER is the most versatile DNA repair mechanism that repairs a wide variety of
DNA lesions through a multistep process involving over 30 different proteins. Being essential to
maintaining genome integrity, this pathway is also highly conserved from yeast to humans.
Genetic defects in NER factors lead to phenotypes ranging from extreme cancer predisposition
syndrome (xeroderma pigmentosum) to severe neurodevelopmental defects (Cockayne
syndrome), thus providing a unique paradigm to understand diverse clinical outcomes of DNA
damage. Recent studies also revealed NER as a major contributor of somatic mutation hotspots
in various sporadic cancers and NER has been suggested as an attractive target for anti-cancer
therapy.
Despite its biological and medical importance, delineating the mechanisms of NER has been a
long-term challenge due to the complex compositions and functions of NER factors and the lack
of comprehensive structural understanding of their interplay on DNA. This proposal aims to define
the mechanism of NER initiation in detailed 3D structures using cryo-EM combined with time-
resolved fluorescence spectroscopy and crosslinking/mass-spectrometry. The outcome will
answer fundamental questions regarding (1) how the two key NER initiators, Rad4-Rad23-Rad33
(yeast homolog of XPC-RAD23B-CETN2) and TFIIH, together start the DNA ‘opening’ around the
damage - a critical step in NER initiation, and (2) how the torsional stress in DNA impacts this
process. This understanding will provide the foundation to explain various pathophysiologies
involving NER, which in turn can lead to novel strategies to counter various NER-linked diseases
including cancer.
Importantly, our research will provide solid training grounds for several undergraduate
researchers every year and will significantly enhance the biomedical research environment at
Baylor University, an undergraduate-focused institution, through its intimate collaboration with
UPenn Medical School. Immersed in an interdisciplinary research project with access to cutting-
edge technologies, our undergraduate researchers will gain expertise in various biochemical and
biophysical approaches and grow as key drivers of significant science.

## Key facts

- **NIH application ID:** 10513526
- **Project number:** 1R15GM147899-01
- **Recipient organization:** BAYLOR UNIVERSITY
- **Principal Investigator:** Jung-Hyun Min
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $377,493
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10513526

## Citation

> US National Institutes of Health, RePORTER application 10513526, Mechanisms of DNA damage processing and the initiation of Nucleotide Excision Repair (1R15GM147899-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10513526. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*