# Role of PALB2 in the DNA Damage Response and Cancer Suppression

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $370,173

## Abstract

Project Summary/Abstract
PALB2 is tumor suppressor protein that physically and functionally links BRCA1 and BRCA2, the two major
breast cancer suppressors, in the DNA damage response and tumor suppression. The 3 proteins function in a
BRCA1-PALB2-BRCA2 axis to play essential roles in in homologous recombination (HR)-based DNA double
strand break repair (DSBR) and cell cycle checkpoint control after DNA damage. These functions are critical
for the maintenance of genome stability and suppressing tumorigenesis. In recent years, much has been
learned about the mechanisms of PALB2 in HR-DSBR, but the mechanisms by which PALB2 functions with
BRCA2 and BRCA1 to promote cell cycle checkpoint response remain elusive, and how normal PALB2 mutant
cells survive and proliferate in vivo and evolve into cancer cells is poorly understood. In this proposal, we will
deploy a combination of state-of-the-art in vitro and in vivo approaches to answer the above open questions. In
Aim 1, we will use phosphoproteomics, targeted proteomics and functional studies to identify key factors and
mechanisms of PALB2-mediated G2/M checkpoint control. In Aim 2, we will build upon our recent discovery of
NFκB activation in Palb2 mutant mice and use a combination of systemic knockin, conditional knockout,
lineage tracing and organoid models to define the mechanisms of PALB2-associated mammary tumorigenesis
and the role of NFκB in the process. In Aim 3, we will determine the genetic mechanisms of our newly
discovered complementary relationship of PALB2 and BRCA1 in mammary tumor development by testing the
roles of RAD52 and RNF168 in the respective models.

## Key facts

- **NIH application ID:** 10870174
- **Project number:** 5R01CA138804-15
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Bing Xia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $370,173
- **Award type:** 5
- **Project period:** 2009-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870174

## Citation

> US National Institutes of Health, RePORTER application 10870174, Role of PALB2 in the DNA Damage Response and Cancer Suppression (5R01CA138804-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10870174. Licensed CC0.

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