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Research ArticleExperimental Studies

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

IOANNIS DRIKOS, EFFROSSYNI BOUTOU, PANAGIOTIS L. KASTRITIS and CONSTANTINOS E. VORGIAS
Anticancer Research June 2021, 41 (6) 2953-2962; DOI: https://doi.org/10.21873/anticanres.15077
IOANNIS DRIKOS
1Deparrtment of Biomedical Sciences, Faculty of Life Sciences, West Attica University, Athens, Greece;
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  • For correspondence: idrikos@uniwa.gr johndrikos@yahoo.com
EFFROSSYNI BOUTOU
2Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece;
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PANAGIOTIS L. KASTRITIS
3Department of Computational Structural Biology, MLU Halle-Wittenberg, Saxony Anhalt, Germany
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CONSTANTINOS E. VORGIAS
2Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece;
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Abstract

Background/Aim: Numerous missense mutations have been determined in the BRCT domain of the BRCA1 gene, affecting localization and interaction of BRCA1 with other proteins. Materials and Methods: 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. Results: 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. Conclusion: 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.

Key Words:
  • BRCA1
  • BRCT
  • mutants
  • cellular localization
  • Received January 10, 2021.
  • Revision received April 24, 2021.
  • Accepted April 26, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (6)
Anticancer Research
Vol. 41, Issue 6
June 2021
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BRCA1-BRCT Mutations Alter the Subcellular Localization of BRCA1 In Vitro
IOANNIS DRIKOS, EFFROSSYNI BOUTOU, PANAGIOTIS L. KASTRITIS, CONSTANTINOS E. VORGIAS
Anticancer Research Jun 2021, 41 (6) 2953-2962; DOI: 10.21873/anticanres.15077

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BRCA1-BRCT Mutations Alter the Subcellular Localization of BRCA1 In Vitro
IOANNIS DRIKOS, EFFROSSYNI BOUTOU, PANAGIOTIS L. KASTRITIS, CONSTANTINOS E. VORGIAS
Anticancer Research Jun 2021, 41 (6) 2953-2962; DOI: 10.21873/anticanres.15077
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Keywords

  • BRCA1
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