BRCA1-BRCT Mutations Alter the Subcellular Localization of BRCA1 In Vitro.

Numerous missense mutations have been determined in the BRCT domain of the BRCA1 gene, affecting localization and interaction of BRCA1 with other proteins. We examined whether the M1775K and V1809F mutations in the BRCT domain affect BRCA1 cellular localization. Cells were transfected with pEGFP-C3-BRCA1 and detected by fluorescence microscopy. Following induction of DNA damage, cytoplasmic mislocalization was observed for both M1775K and V1809F mutants compared to EGFP-BRCA1wt and the less common variant M1652I. These results indicate that M1775K and V1809F mutations may change the function of the protein by affecting BRCA1 localization. There is a correlation between subcellular localization of BRCA1 and diminished DNA repair observed in breast cancer cells, which may be explained by structural variations and altered binding properties of phosphopeptides. Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Citation

Ioannis Drikos, Effrossyni Boutou, Panagiotis L Kastritis, Constantinos E Vorgias. BRCA1-BRCT Mutations Alter the Subcellular Localization of BRCA1 In Vitro. Anticancer research. 2021 Jun;41(6):2953-2962

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PMID: 34083286

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