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Role of BRCA2 DNA-binding and C-terminal domain in its mobility and conformation in DNA repair.
Paul, Maarten W; Sidhu, Arshdeep; Liang, Yongxin; van Rossum-Fikkert, Sarah E; Odijk, Hanny; Zelensky, Alex N; Kanaar, Roland; Wyman, Claire.
Afiliación
  • Paul MW; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Sidhu A; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Liang Y; Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, Netherlands.
  • van Rossum-Fikkert SE; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Odijk H; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Zelensky AN; Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Kanaar R; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
  • Wyman C; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
Elife ; 102021 07 13.
Article en En | MEDLINE | ID: mdl-34254584
Breast cancer type two susceptibility protein (BRCA2) is an essential protein in genome maintenance, homologous recombination (HR), and replication fork protection. Its function includes multiple interaction partners and requires timely localization to relevant sites in the nucleus. We investigated the importance of the highly conserved DNA-binding domain (DBD) and C-terminal domain (CTD) of BRCA2. We generated BRCA2 variants missing one or both domains in mouse embryonic stem (ES) cells and defined their contribution in HR function and dynamic localization in the nucleus, by single-particle tracking of BRCA2 mobility. Changes in molecular architecture of BRCA2 induced by binding partners of purified BRCA2 were determined by scanning force microscopy. BRCA2 mobility and DNA-damage-induced increase in the immobile fraction were largely unaffected by C-terminal deletions. The purified proteins missing CTD and/or DBD were defective in architectural changes correlating with reduced HR function in cells. These results emphasize BRCA2 activity at sites of damage beyond promoting RAD51 delivery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína BRCA2 / Proteínas de Unión al ADN / Reparación del ADN / Conformación de Ácido Nucleico Límite: Animals / Humans Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína BRCA2 / Proteínas de Unión al ADN / Reparación del ADN / Conformación de Ácido Nucleico Límite: Animals / Humans Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido