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

Autor:	Effrossyni Boutou, Panagiotis L Kastritis, Ioannis Drikos, Constantinos E. Vorgias
Rok vydání:	2021
Předmět:	Cancer Research endocrine system diseases DNA repair Chemistry DNA damage Mutant General Medicine Transfection Subcellular localization Cell biology BRCT domain Oncology Cytoplasm skin and connective tissue diseases Cellular localization
Zdroj:	Anticancer Research. 41:2953-2962
ISSN:	1791-7530 0250-7005
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::d914a557061dc37b57590363395c4016 https://doi.org/10.21873/anticanres.15077 Zobrazit plný text záznamu