# Dissecting BRCA1-PALB2 Activity in DNA Repair and Development

> **NIH NIH R01** · RESEARCH INST OF FOX CHASE CAN CTR · 2021 · $229,000

## Abstract

PROJECT SUMMARY/ABSTRACT
This submission is for a supplement award for the parent grant R01GM135293: “Dissecting BRCA1-PALB2
activity in DNA repair and development”. The parent grant is currently in its first year, making this the perfect
time to upgrade our equipment. The localization of proteins to double stranded DNA breaks (DSBs) can be
quantified by the presence of nuclear foci. The number of foci within a nucleus is often indicative of whether a
particular protein or repair pathway is functional. A typical focus appears as a homogenous sphere under
conventional widefield or confocal microscopy. The information provided does not go beyond whether foci are
present or absent. In contrast, super-resolution (SR) microscopy provides high-resolution imagining, which can
reveal detailed insights into the DSB-flanking chromatin topology. The ability to perform SR microscopy would
greatly enhance the knowledge that can be gained from the current R01-funded project. Not only in
understanding the effects of mutations on foci formation, new insights into the mechanics of the DNA damage
repair machinery and the interplay between chromatin topology and DNA repair can be revealed. In the parent
grant, we aim to uncover the mechanisms by which BRCA1 recruits PALB2 to sites of DNA damage. We
proposed to examine the effects of BRCA1 and PALB2 mutations on DNA repair foci. However, SR microscopy
has the potential to reveal so much more, beyond simply the presence or absence of foci, such as insights into
the nanostructure of BRCA1-PALB2, whether there are separate or overlapping nanodomains, spatial
differences, and the BRCA1-PALB2 topology relative to additional homologous recombination (HR) proteins.
Moreover, the effects of BRCA1 and PALB2 patient mutations have previously not been examined for their
effects on DSB-chromatin topology and nanostructure. The use of SR microscopy will provide super-resolution
insight, and ultimately improve our understanding of how BRCA1 and PALB2 mutations impact human health.

## Key facts

- **NIH application ID:** 10388570
- **Project number:** 3R01GM135293-02S1
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **Principal Investigator:** Neil Johnson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $229,000
- **Award type:** 3
- **Project period:** 2020-08-05 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388570

## Citation

> US National Institutes of Health, RePORTER application 10388570, Dissecting BRCA1-PALB2 Activity in DNA Repair and Development (3R01GM135293-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10388570. Licensed CC0.

---

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