# Dynamics and Regulation of Chromatin in DNA Metabolism

> **NIH NIH R35** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $395,451

## Abstract

PROJECT SUMMARY
The nucleotide excision repair (NER) pathway is the main pathway responsible for the removal
of bulky DNA lesions such as those formed by UV irradiation. It is highly conserved and its
deregulation is linked to human disorders such as xeroderma pigmentosum. In cells, NER does
not occur on naked DNA templates, but on a DNA-protein complex called chromatin. The
integrity and the structure-dynamics of chromatin are fundamental to the normal function and
survival of all eukaryotes. Changes in chromatin architecture directly influence genome
accessibility and thus nuclear processes such as DNA damage repair via NER. Yet our
knowledge of how NER occurs in its native environment, chromatin is limited. Emerging
evidence indicates the important role of two key chromatin regulator in modulating chromatin
dynamics to facilitate damage repair in NER. These two regulators are the INO80 ATP-
dependent chromatin remodeler and the heterochromatin protein 1. More importantly, the
functions of these proteins in NER appear to be at least in part due to their ability to interact with
either NER repair factors (e.g. UV-DDB complex) and/or chromatin structural components (e.g.
histone variant H2A.Z).
 To elucidate the molecular mechanism of chromatin structure-dynamics regulation and how
it is coupled to DNA damage repair, we will use a combination of single-particle cryo-electron
microscopy (EM), traditional biochemistry and biophysical techniques to address the following
questions: (1) what is the structural basis of chromatin folding mediated by histone variant
H2A.Z? (2) What is the structural mechanism of chromatin compaction by linker histone H1? (3)
How is preexisting chromatin environment impact lesion detection in the NER pathway? (4) Do
photo lesions on nucleosome interfere with INO80-mediated ATP-dependent chromatin
remodeling and what is the mechanism of INO80 recruitment to photo lesions? (5) What is the
molecular and structural mechanism of HP1 targeting to photo lesion on chromatin? Overall, this
work will greatly improve our understanding of the role chromatin play in genome surveillance
system. It will also provide critical insights into how regulation of chromatin structure-dynamics
via either histone proteins or chromatin associated factors influence key steps during repair.

## Key facts

- **NIH application ID:** 10001586
- **Project number:** 5R35GM133611-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Dongyan Tan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,451
- **Award type:** 5
- **Project period:** 2019-09-07 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001586

## Citation

> US National Institutes of Health, RePORTER application 10001586, Dynamics and Regulation of Chromatin in DNA Metabolism (5R35GM133611-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001586. Licensed CC0.

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