# Deciphering the chromatin-based DNA damage response pathway

> **NIH NIH R35** · UNIV OF ARKANSAS FOR MED SCIS · 2021 · $380,000

## Abstract

PROJECT SUMMARY
DNA damage is a constant threat to our genome. Our body has evolved a surveillance mechanism, namely the
DNA damage response (DDR) pathway, to protect our cells from genotoxic insults. Defective DDR pathway leads
to unfaithful repair of DNA breaks which results in accumulation of mutations, chromosome rearrangement, and
genome instability. Although much is known about how chromatin senses and responds to DNA damage, a
significant gap in knowledge exists with the poorly characterized mechanism by which damaged chromatin
transduces the signal to recruit effector proteins to DNA breaks. Such knowledge is imperative to understand
how cells precisely execute the correct pathway by recruiting the right repair protein complex in a temporal and
spatial manner which is essential for maintaining our genome integrity. This research program aims to address
this fundamental question in the chromatin-based DDR pathway. Our expertise lies in genome editing, functional
proteomics, molecular biology, cell biology, and biochemistry. We combine our techniques of protein purification,
confocal microscopy, laser-induced single cell micro-irradiation, cell-based reporter assays, protein tagging, and
quantitative mass spectrometry for an overall multidisciplinary approach. The goals of this MIRA project are to
obtain a comprehensive molecular understanding of the chromatin-based DDR pathway by 1) determining the
epigenetic profile in the DDR pathway, 2) characterizing the functions of the novel DNA repair proteins and 3)
elucidating the mechanism of how damaged chromatin orchestrates different DNA repair pathways during the
cell cycle in the context of damaged chromatin. Using fractionation purification-coupled proteomic approach and
cell-based functional assays, we have identified more than twenty novel DNA repair proteins. Our long-term
goals are to build a physical and genetic network within the chromatin-based DDR pathway and understand its
impact in human health. Overall, these studies will open up a new arena for the DNA repair field, provide insight
into the etiology of cancer and genome instability-related genetic diseases that will lay the foundation for
translational research and therapeutic strategy development.

## Key facts

- **NIH application ID:** 10247749
- **Project number:** 5R35GM137798-02
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Justin Wai Chung Leung
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247749

## Citation

> US National Institutes of Health, RePORTER application 10247749, Deciphering the chromatin-based DNA damage response pathway (5R35GM137798-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247749. Licensed CC0.

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