Role of Sgs1, yeast Werner/Bloom homologue in DNA repair

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DESCRIPTION (provided by applicant): DNA repair and recombination is crucial for the fidelity of DNA replication. The RecQ family of DNA helicases is required for this process and in humans, mutations in these genes leads to the Bloom's, Werner's, and Rothmund-Thomson syndromes. All of these diseases are fundamentally characterized by a predisposition to cancer due to chromosomal loss and rearrangement. In yeast, the Sgs1 protein, is the only homologue to the human RecQ family of DNA helicases. Mutations in this protein recapitulate the affects observed with the human diseases suggesting that its functions have been conserved to humans. Due to the vast ease of doing genetics, cellular biology, and molecular biochemistry in yeast, this model organism is ideal to study this family of DNA helicases. Outlined here, I plan to further characterize the role of the Sgs1 protein in the DNA repair pathway and to find and characterize additional interacting proteins to Sgs1. Using techniques developed in the Rothstein laboratory, I will be able to further understand the mechanism of how the Sgs1 protein leads to cancer development in higher eukaryotes.