Northwestern University

Feb
23
Thu 10:00 AM

BMG Seminar: Beta-catenin mediated genomic instability in T cell leukemia - Fotini Gounari, PhD, DSc

When: Thursday, February 23, 2017
10:00 AM - 11:00 AM  

Where: Robert H Lurie Medical Research Center, Searle Seminar Room, 303 E. Superior, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Carson Nestler   (312) 503-5229

Group: Biochemistry & Molecular Genetics Seminar Series

Category: Lectures & Meetings

Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Fotini Gounari, PhD, DSc
Associate Professor, Department of Medicine
The University of Chicago

Genomic instability and cancer cell plasticity are major obstacles to effective cancer treatment. A driving force of genomic instability in a number of common cancers including solid tumors and hematologic malignancies is the aberrant activation of β-catenin signaling. We have studied these mechanisms in a β-catenin driven mouse model of T-cell leukemia/lymphoma. Lymphomas that arise in these mice have a wide range of chromosomal defects as well as recurrent translocations of the T-cell receptor-alpha to the cMyc linked non-coding break point region, the Pvt1-locus. This is a highly relevant model as the Myc-Pvt1 locus is commonly targeted for translocations in human hematopoietic and solid cancers. We found that the translocations result from the illegitimate joining of desynchronized chromosomal breaks; breaks which normal physiology occur in two different cell cycle checkpoints. Indeed stabilization of β-catenin in pre-leukemic thymocytes, enhanced chromatin accessibility, down-regulated cell cycle checkpoint and recombination repair genes, and enhanced survival. Our findings suggest that aberrant activation of β-catenin promotes genomic instability through epigenetic and transcription events that alter replication, compromise replication checkpoints and homology directed repair of replication induced DNA breaks and enhance survival of cells with damaged DNA.

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