# Collaborative Functions of BRCA2 and RAD51 Paralogs in Homologous recombination

> **NIH NIH R21** · YALE UNIVERSITY · 2023 · $209,375

## Abstract

PROJECT SUMMARY
Despite several years of investigation, the human RAD51 paralogs: RAD51B, RAD51C, RAD51D, XRCC2, and
XRCC3 remain enigmatic proteins required for cell viability and homology-directed repair (HDR) of DNA
double-strand breaks (DSBs). The RAD51 paralogs have been found to exist in two protein complexes within
human cells: RAD51B/RAD51C/RAD51D/XRCC2 and RAD51C/XRCC3. Our preliminary data indicate that the
RAD51 paralogs interact with BRCA2 in a specific orientation likely important for mechanistic control over the
RAD51 nucleoprotein filament. Our objective in this proposal is to address the biochemical and genetic
relationship between BRCA2 and the RAD51 paralogs in response to DNA damage. Our hypothesis is that
BRCA2 and the RAD51 paralogs work together in the pre- or post-synaptic phase of HDR to either enhance
RAD51 nucleoprotein filament stability or to stimulate strand invasion and the homology search. We will map
the sites of interaction between BRCA2 and the RAD51 paralogs. We will determine whether interactions are
regulated by DNA damage and what impact the BRCA2/RAD51 paralog complex has on RAD51 filament
dynamics. We have developed human cell systems from which to purify the RAD51 paralog proteins
individually or in complexes (B/C/D/X2 and C/X3). These purified proteins will then be used for biochemical
studies of HDR. BRCA2 has been linked to stabilization of replication forks to prevent nucleolytic degradation
under conditions of cellular stress, and therefore, we will determine whether the RAD51 paralogs cooperate
with BRCA2 to stabilize RAD51 at stalled replication forks through analyses of DNA fibers and super-resolution
microscopy. In summary, we plan to use both biochemical and genetic approaches to understand the interplay
between BRCA2 and the RAD51 paralogs and how defects in these proteins lead to genomic instability and
cancer.

## Key facts

- **NIH application ID:** 10608155
- **Project number:** 5R21ES034164-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Ryan Brown Jensen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2022-04-11 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10608155

## Citation

> US National Institutes of Health, RePORTER application 10608155, Collaborative Functions of BRCA2 and RAD51 Paralogs in Homologous recombination (5R21ES034164-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10608155. Licensed CC0.

---

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