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GEWONE VERGADERING DER LEDEN VAN HET BATAAFSCH GENOOTSCHAP DER PROEFONDERVINDELIJKE WIJSBEGEERTE TE ROTTERDAM OP MAANDAG 9 JANUARI 2017 TE 20.00 UUR In de zaal SH 2 van het Raadhuis (ingang B via poort) Spreker: Mw.Prof.dr. Claire Wyman Department of Radiation Oncology and Molecular Genetics, Erasmus MC ONDERWERP : “ The Molecular Machines of DNA break repair, nanoscale events in carcinogenesis” We are discovering how proteins work together in complex and dynamic assemblies that accomplish the work of living cells. We determine how proteins assemble into functional nanomachinery when and where they are needed. Understanding the details of normal molecular function, how this is disturbed in disease processes and how it can be modulated therapeutically is essential for progress and advancement in medicine. My work currently addresses genome maintenance by DNA repair processes, specifically DNA break repair by homologous recombination. Homologous recombination is a process that depends on sequential action of many enzymes to repair DNA structure while avoiding inappropriate DNA rearrangements. The BRCA2 tumor suppressor protein is one of the essential players in the process of homologous recombination repair of double strand breaks. We take advantage of technical advances to image isolated BRCA2 with nanometer resolution and follow its behavior in live cells. We have discovered and quantified structural features and activities of BRCA2 and can determine if existing BRCA2 variants, such as human variants of unknown significance, are disturbed in these features. Unraveling mechanistic details of this essential genome maintenance pathway helps us understand how cancer develops and is potentially useful for designing improved anti-cancer treatments.