# The role of a BRCA1 associated complex in DNA damage response and tumor suppression

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $380,000

## Abstract

ABSTRACT
 The hereditary breast and ovarian cancer tumor suppressor protein BRCA1 plays critical roles in
DNA repair, cell cycle checkpoint control, and maintenance of genomic stability. BRCA1 is recruited to DNA
damage sites through a BRCA1-associated complex, the BRCA1-A complex in response to ionizing
radiation. Abraxas is the central adaptor protein in the BRCA1-A complex and binds to BRCA1 BRCT
domains in a phosphorylation-dependent manner. We have demonstrated that Abraxas plays an important
role in suppressing tumor development in mice and that the interaction between Abraxas and BRCA1 is
critical for Abraxas' function in repair of DNA and maintenance of genome stability, indicating that Abraxas
is part of BRCA1 signaling in breast tumor suppression. Focusing on the role of Abraxas in ionizing
radiation-induced double strand break repair and elucidating the regulatory mechanism for Abraxas's
function will provide insights into the role of Abraxas as a novel tumor suppressor gene and will uncover
novel mechanisms important for its tumor suppressor function. In this application, we will first investigate a
novel mechanism regulating Abraxas-mediated BRCA1 accumulation at DNA double strand breaks through
double-phosphorylation of the C-terminus of Abraxas in response to ionizing radiation. Second, we will
examine the tumor-related somatic mutations of Abraxas and determine the regulatory mechanisms for the
function of Abraxas in suppressing genomic instability and tumor development. Third, we will determine the
role of Abraxas in breast tumor suppression by generating and examining mammary-specific Abraxas-
deficient mouse models. Together, our study will determine the role of Abraxas as a tumor suppressor gene
and the regulatory mechanisms for its tumor suppressor function. It will provide new insights into the causes
and mechanisms of breast cancer and may lead to the discovery of new therapies for Abraxas-deficient
breast cancer.

## Key facts

- **NIH application ID:** 9998847
- **Project number:** 5R01CA155025-10
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Bin Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2011-03-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998847

## Citation

> US National Institutes of Health, RePORTER application 9998847, The role of a BRCA1 associated complex in DNA damage response and tumor suppression (5R01CA155025-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9998847. Licensed CC0.

---

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