Structural and biochemical characterization of the.. (BRCA2complexes)
Structural and biochemical characterization of the BRCA2 breast cancer tumour suppressor
Start date: Apr 1, 2014,
End date: Mar 31, 2016
Our genetic material is constantly exposed to mutagenic factors. DNA double-strand breaks (DSBs) represent one of the most dangerous forms of DNA damage and cells utilise two major pathways for their repair: error-prone non-homologous end-joining (NHEJ) and error-free homologous recombination (HR). The breast cancer susceptibility protein BRCA2 is a central player in HR that cooperates with its partner PALB2 in promoting the recruitment of RAD51 recombinase to the site of DNA damage. BRCA2 function is essential for the maintenance of genome integrity and mutations in the BRCA2 gene have been linked to breast and ovarian cancer, and to the cancer-prone syndrome Fanconi anemia.To obtain new insights into how various aspects of homology-directed repair are coordinated by BRCA2 and its cofactors I intend to:1. Characterize the structural properties of BRCA2 together with its partners RAD51 and PALB2, in order to identify important interaction regions.2. Define the functional relevance of these interaction sites using a combination of biochemical and in vivo techniques to uncover the molecular mechanism of BRCA2-mediated DNA repair and to address the specific roles of its partner proteins RAD51 and PALB2.The results will be important for understanding the molecular basis of BRCA2-associated pathogenesis.
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