BARD1 and Breast Cancer: The Possibility of Creating Screening Tests and New Preventive and Therapeutic Pathways for Predisposed Women.

Marcin Śniadecki,Marta Krzeszowiec,Dagmara Klasa-Mazurkiewicz,Patryk Poniewierza,Natalia Kmieć,Katarzyna Darecka,Michał Brzeziński,Dariusz Wydra

doi:10.3390/genes11111251

Marcin Śniadecki, Marta Krzeszowiec + Show 6 more

Open Access

https://doi.org/10.3390/genes11111251

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Journal: Genes	Publication Date: Oct 24, 2020
Citations: 15	License type: CC BY 4.0

Affiliation: Gdańsk Medical University, University Clinical Centre

Abstract

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the one of these genes, BRCA1-associated RING domain protein 1 (BARD1), and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 (BReast CAncer type 1) proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. The BARD1-BRCA1 complex is involved in genetic stabilization at the cellular level. It allows to mark abnormal DNA fragments by attaching ubiquitin to them. In addition, it blocks (by ubiquitination of RNA polymerase II) the transcription of damaged DNA. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

Highlights

In 1996, Wu et al discovered a binding partner protein of BRCA1 (BReast CAncer type 1)which they named BRCA1-associated RING domain 1 (BARD1) [1]
We focused on four main issues regarding BRCA1-associated RING domain protein 1 (BARD1)
The first one discusses the frequency of mutations in the BARD1 gene in non-BRCA1 and non-BRCA2 patients with breast cancer

Summary

Introduction

Which they named BRCA1-associated RING domain 1 (BARD1) [1]. 22 of of 12 composed of an N‐terminal RING‐finger domain, three Ankyrin repeats (ANK) domains, and two composed of an N-terminal RING-finger domain, three Ankyrin repeats (ANK) domains, and two tandem BRCA1 C‐terminal (BRCT) domains (Figure 1). The BARD1 protein structure is like that of tandem BRCA1 C-terminal (BRCT) domains (Figure 1). The BARD1 protein structure is like that of the BRCA1, it is different from that of the BRCA2 (BReast CAncer type 2), the second gene the BRCA1, it is different from that of the BRCA2 (BReast CAncer type 2), the second gene associated with breast cancer [2]. BARD1 and BRCA1 can form a heterodimer by their N‐terminal associated with breast cancer [2]. BARD1 and BRCA1 can form a heterodimer by their N-terminal

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