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

Sgs1（酵母 Werner/Bloom 同源物）在 DNA 修复中的作用

• 批准号: 7280478
• 负责人: Kara A Bernstein
• 金额: $ 4.6万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7280478
• 关键词: Address; Affect; Animal Model; Biochemical Genetics; Biochemistry; Biological; Biological Models; Cancer Etiology; Cell physiology; Cells; Chromosomal Loss; Cyclophosphamide/Fluorouracil/Prednisone; DNA Damage; DNA Repair; DNA Repair Pathway; DNA Sequence Rearrangement; DNA biosynthesis; DNA repair protein; DNA strand break; Development; Disease; Ensure; Eukaryota; Eukaryotic Cell; Family; Family Study; Frequencies; Genes; Genetic; Genetic Recombination; Genomics; Growth; Hereditary Disease; Homologous Gene; Human; Label; Laboratories; Lead; Localized; Maintenance; Malignant Neoplasms; Methodology; Methyl Methanesulfonate; Microscopy; Molecular and Cellular Biology; Mutation; Numbers; Partner in relationship; Pathway interactions; Phase; Phenotype; Plasmids; Predisposition; Procedures; Process; Protein Fragment; Proteins; Role; Rothmund-Thomson syndrome; Saccharomyces cerevisiae; Sgs1 protein; Syndrome; Techniques; Technology; Yeast Model System; Yeasts; base; chromosome 2 loss; deletion library; dosage; helicase; human disease; hydroxyurea; novel; novel strategies; repaired; research study; time use; vector

DNA repair and recombination is crucial for the fidelity of DNA replication. The RecQ family of DMA 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.

DNA修复和重组对于DNA复制的保真度至关重要。RecQ系列DMA 解旋酶是这一过程所必需的，在人类中，这些基因的突变导致布卢姆氏病， 维尔纳综合征和Rothmund-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而易患癌症。在酵母中，Sgs 1蛋白是唯一 与人RecQ DNA解旋酶家族同源。这种蛋白质的突变重现了 在人类疾病中观察到，表明其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非常容易，这种模式生物是 非常适合研究这个DNA解旋酶家族。在这里，我计划进一步描述Sgs 1的作用 蛋白质在DNA修复途径，并找到和表征其他相互作用的蛋白质Sgs 1。使用 在罗斯坦实验室开发的技术，我将能够进一步了解如何机制 Sgs 1蛋白导致高等真核生物中的癌症发展。