# RAD51 paralog function in cancer predisposition and genome integrity > **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $469,943 ## Abstract Project Summary/Abstract: Accurate repair of DNA damage is critical for genetic stability, and for preventing aging-related degeneration and cancer. We are working to identify key factors that regulate accurate repair of DNA double-strand breaks (DSBs) through the error-free homologous recombination (HR) pathway. DSBs can arise from many sources including endogenous replication fork damage, exogenous environmental toxicants, or oxidative stresses induced by endogenous sources and during pro-inflammatory responses to toxicant injury. We found that the RAD51 paralogs are critical for promoting HR and hence for suppressing error-prone repair mechanisms. Over 300 studies link mutations in human RAD51 paralogs with cancer, and women with breast or ovarian cancer are now screened for RAD51 paralog mutations. However, it remains largely unknown which RAD51 paralog mutations are pathogenic and how these mutations sensitize individuals to environmentally induced-DNA damage due to our lack of functional analysis of either the wild-type or mutated proteins. We do not know how these proteins are recruited, their functional components, or the disruptions caused by mutations or polymorphisms in the RAD51 paralogs. This knowledge gap results from low abundance of endogenous RAD51 paralog proteins, insolubility of the recombinant proteins, as well as embryonic lethality in knock-out mice. We are therefore using genetic, biochemical, and cell biological approaches to characterize RAD51 paralog function upon exposure to DSB inducing agents. We will use ionizing radiation (IR) and bleomycin as model agents for environmentally relevant DSB-inducing agents. Using complementary approaches in combination with high-throughput genetic screening, we are now uniquely poised to address how RAD51 paralog mutations predispose individuals to human cancer and thus, to identify opportunities for determining who is at risk for cancer development upon exposure to environmental carcinogens. Our ultimate goal is to enable development of precision medicine strategies for individual patients whose tumors harbor a RAD51 paralog mutation profile. ## Key facts - **NIH application ID:** 10372159 - **Project number:** 5R01ES031796-02 - **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH - **Principal Investigator:** Kara A Bernstein - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $469,943 - **Award type:** 5 - **Project period:** 2021-03-15 → 2022-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10372159 ## Citation > US National Institutes of Health, RePORTER application 10372159, RAD51 paralog function in cancer predisposition and genome integrity (5R01ES031796-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10372159. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*