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

描述（申请人提供）：DNA修复和重组对DNA复制的保真度至关重要。DNA解旋酶的RecQ家族在这一过程中是必需的，在人类中，这些基因的突变会导致Bloom综合征、Werner综合征和rothmond - thomson综合征。所有这些疾病的基本特征都是由于染色体丢失和重排导致易患癌症。在酵母中，Sgs1蛋白是唯一与人类DNA解旋酶家族同源的。这种蛋白的突变概括了在人类疾病中观察到的影响，表明它的功能对人类是保守的。由于在酵母中进行遗传学，细胞生物学和分子生物化学的巨大便利，这种模式生物是研究DNA解旋酶家族的理想选择。在这里概述，我计划进一步表征Sgs1蛋白在DNA修复途径中的作用，并发现和表征其他与Sgs1相互作用的蛋白。利用罗斯坦实验室开发的技术，我将能够进一步了解Sgs1蛋白如何导致高等真核生物癌症发展的机制。

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.