Analysis of the Relationship between PARP1 and BRCA1 Suggests PARP1 Gene Has a Role in Breast Cancer

Abstract

Poly [ADP-ribose] polymerase 1 (PARP1), one of the genes in the PARP family, is mainly involved in the detection and repair of DNA damage in cells, and its upregulation has been associated with tumorigenesis. PARP1 is essential to all cells in the body as it ensures that DNA is replicated correctly. The PARP1 protein addresses repair of single-stranded breaks (SSBs) in DNA by initially binding near the point of break in the DNA. While it is bound to the region of the SSB, PARP1 transfers ADP ribosyl moiety from NAD+ to acceptor proteins. This leads to the recruitment of DNA repair proteins to the region of DNA breaks. The PARP1 protein also aids the double-stranded break (DSB) repair of DNA by recruiting the homologous recombination (HR) pathway proteins. Due to this role of PARP1 in DNA repair, it has been associated with cancer growth. Using databases, including UniProt, Xena Browser, and CBioPortal, this article explores the relationship between PARP1 mutations and BRCA1-mutated breast cancer. BRCA1 is a tumor suppressor gene, which is involved in DNA repair through the HR pathway. Therefore, in BRCA1-mutated cells, the lack of tumor suppressor factors leads to cancer growth. However, in a cell that has both BRCA1 mutations and PARP1 inhibition, DNA damage cannot be repaired, leading to apoptosis. Hence, PARP1 inhibitors have become essential in BRCA1-mutated breast cancers. There are several PARP1 inhibitors that are currently being used to treat breast cancer, which work using several mechanisms of action, including PARP1 trapping, which prevents the repair, transcription, and replication of DNA. This article also focuses on the clinical trials of three specific drugs, Olaparib, Iniparib, and Veliparib, which are used to treat breast cancer. However, due to the lack of understanding surrounding PARP1 inhibition mechanisms and potential drug combinations, more research needs to be done to understand potential biomarker targets and PARP1 inhibitor resistance.