# Determining the effects of RAD51C ovarian cancer variants

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $46,752

## Abstract

Project Summary/ Abstract
Approximately 50% of high grade serous ovarian cancers (HGSOC) are deficient in homologous recombination
(HR). HR is a high-fidelity DNA double-strand break repair pathway which uses a homologous template for
accurate DNA repair. The central protein of this process, RAD51, is tightly regulated. One group of proteins
that work to regulate RAD51 are the RAD51 paralogs, including RAD51C and RAD51D. Collectively, RAD51C
and RAD51D are mutated in 8% of HR deficient familial ovarian cancers. Although the RAD51 paralogs were
discovered 20+ years ago their exact function in HR, and how mutation in these proteins contribute to HGSOC
is still unknown. We have identified two possible RAD51C protein isoforms which may perform separate
function in HR. RAD51C variants that would prevent protein production of either isoform have been identified in
32 separate individuals. Thus, we propose a functional analysis of these isoforms and mutations which disrupt
their production. In addition, we have also identified mutations in RAD51C which disrupt its interaction with
RAD51D. Our preliminary data has determined that the yeast-three-hybrid interaction between RAD51C and
RAD51D is a good indicator of HR efficiency in human cells. Yet, how this RAD51C-RAD51D interaction
contributes to HR is still unknown. We will examine the effects of these variants on RAD51 protein regulation
and filament dynamics using single-molecule fluorescence microscopy (C-trap). By characterizing the activity
of these RAD51C variants we will uncover both the function of WT-RAD51C and how dysfunctional RAD51C
variants contribute to HR deficiency in HGSOC.

## Key facts

- **NIH application ID:** 10461516
- **Project number:** 1F31CA264889-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Hayley Rein
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461516

## Citation

> US National Institutes of Health, RePORTER application 10461516, Determining the effects of RAD51C ovarian cancer variants (1F31CA264889-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10461516. Licensed CC0.

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