# BRCA1 and the regulation of chromatin dynamics in gene expression

> **NIH NIH R35** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $421,978

## Abstract

Project Summary
BRCA1 is an established tumor suppressor that plays a critical role in the development of both sporadic and
hereditary breast and ovarian cancer. Considered a “master regulator” of genome integrity, BRCA1 has been
linked to nearly all aspects of chromatin biology. Loss of BRCA1 is embryonic lethal and leads to cellular
defects in stress signaling, DNA repair, cell cycle progression, apoptosis, chromatin condensation, and gene
expression. Each of these processes involves dynamic changes in chromatin architecture that regulate spatial
and temporal access to genomic DNA. Although implicated in various mechanisms of chromatin modification
and remodeling, a mechanistic understanding of BRCA1’s role in regulating chromatin dynamics has been
difficult to establish due to the global consequences of its dysfunction. Recently, we established a cell-free
system that supports transcription of naturally chromatinized plasmid substrates in Xenopus egg extract.
Transcriptional activity in extract is tightly coupled to changes in chromatin modification and structure,
providing a powerful tool to study how regulation of chromatin dynamics controls gene expression. By coupling
this system with established approaches used to elucidate mechanisms of DNA replication and DNA repair, we
are now poised to examine the interplay between these fundamental processes. Indeed, BRCA1’s role as a
sensor for genomic stress places it at the center of genome utilization, maintenance, and repair. In this
proposal, we seek to understand how BRCA1 and other chromatin regulators control access to DNA in
response to different cellular events. Together, these studies will provide new mechanistic insight into the
complexities of chromatin signaling that remain an essential, but poorly understood regulator of genome
integrity.

## Key facts

- **NIH application ID:** 10842372
- **Project number:** 5R35GM119512-09
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** David Thomas Long
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $421,978
- **Award type:** 5
- **Project period:** 2016-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842372

## Citation

> US National Institutes of Health, RePORTER application 10842372, BRCA1 and the regulation of chromatin dynamics in gene expression (5R35GM119512-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842372. Licensed CC0.

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