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The Department of Biochemistry and Molecular Genetics: "The balance between Tcf-1 and beta-catenin is critical to secure genome stability in thymocytes"

Event Type
Other
Sponsor
Presented by the Department of Biochemistry and Molecular Genetics
Location
Molecular Biology Research Building, Herman Auditorium
Date
Dec 12, 2012   12:00 - 1:00 pm  
Speaker
Dr. Fotini Gounari, Knapp Center for Lupus and Immunology Research, University of Chicago
Views
160
Originating Calendar
CCTS Events

Title: "The balance between Tcf-1 and beta catenin is critical to secure genome stability in thymocytes"

Speaker: Dr. Fotini Gounari, Knapp Center for Lupus and Immunology Research, University of Chicago

The T-cell specific HMG domain factor Tcf-1 depends on its interaction with β-catenin to promote gene transcription. We show here that Tcf-1, one of the most abundantly expressed genes in double positive (DP) thymocytes, binds actively transcribing loci despite limiting amounts of β-catenin. Tcf-1, and RAG2 overlap at common histone-3-tri-methylated at lysine-4 chromatin sites genome-wide. In addition, Tcf-1 binds the DNA-repair protein Ku70 and elevated b-catenin levels outcompete this interaction resulting in altered resolution of RAG induced DNA-double-strand-breaks and increased DNA-damage.  At the same time, elevated b-catenin levels enable survival of cells with damaged DNA. This combination culminates in RAG-dependent lymphomas with recurring Tcra/Myc oncogenic translocations. Our findings reveal a novel Tcf-1 function in DNA-repair that is controlled by b-catenin and

suggest how it can be compromised in carcinogenesis.

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