Functional analyses of rare germline BRCA1 variants by transcriptional activation and homologous recombination repair assays.

ABSTRACT:

Background

Damaging alterations in the BRCA1 gene have been extensively described as one of the main causes of hereditary breast and ovarian cancer (HBOC). BRCA1 alterations can lead to impaired homologous recombination repair (HRR) of double-stranded DNA breaks, a process which involves the RING, BRCT and coiled-coil domains of the BRCA1 protein. In addition, the BRCA1 protein is involved in transcriptional activation (TA) of several genes through its C-terminal BRCT domain.

Methods

In this study, we have investigated the effect on HRR and TA of 11 rare BRCA1 missense variants classified as variants of uncertain clinical significance (VUS), located within or in close proximity to the BRCT domain, with the aim of generating additional knowledge to guide the correct classific

SUBMITTER: Bassi N 

PROVIDER: S-EPMC10122298 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature