GENETIC CONTROL OF NUTRITIONAL STARVATION IN YEAST

酵母营养饥饿的基因控制

• 批准号: 6046024
• 负责人: GERALD R FINK
• 金额: $ 49.22万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6046024
• 关键词: Saccharomyces cerevisiae; cell cycle; cell proliferation; cytogenetics; deficient growth media; flow cytometry; fungal genetics; gene expression; genetic regulation; genetic regulatory element; genetic transcription; haploidy; polyploidy; posttranslational modifications; regulatory gene; salts; starvation

Experiments are designed to determine the mechanism by which gene expression is controlled by ploidy in the yeast Saccharomyces cerevisiae. This work has implications for abnormal cell growth in humans because tumor cells with aberrant cell control often contain an abnormal number of chromosomes. Although hyperploidy is usually viewed as a consequence of aberrant cell cycle control, this proposal suggests that hyperploidy itself may cause the abnormal expression of key molecules required for cell proliferation. Gene arrays will be used to determine the molecular basis for the ploidy control of gene transcription in isogenic yeast strains whose ploidy varies from haploid to tetraploid. One set of experiments is designed to identify the role of G1 cyclin transcription in the ploidy control of cell size and cell proliferation. These studies will determine whether ploidy control is itself cell cycle regulated. As polyploid cells are much more sensitive to nutritional starvation that their euploid counterparts, the genes responsible for the differences in euploid and polyploid growth control will be identified. The role of heterozygosity at the mating type locus and chromosome pairing in the response of polyploids to nutritional starvation will be ascertained. The promoter of one of the genes known to be transcriptionally controlled by ploidy will be analyzed to identify cis-acting sequences that respond to ploidy control. Another screen is designed to identify the trans-acting genes that mediate ploidy control. Salt resistance, a ploidy sensitive phenotype, will be used to screen for suppressors of the ploidy dependent phenotype. In addition the cellular basis for salt sensitivity will be elucidated. A third set of experiments identifies the role of the Rim1 transcription factor in stationary phase metabolism. This yeast homolog of a known fungal regulator of penicillin production is proposed to control stationary phase metabolism in Saccharomyces. A fourth set of experiments focuses on the role of dipthamide, a conserved posttranslational modification of elongation factor2 in cellular regulation. dph mutants have a stationary phase defect that is again more severe in diploids that in haploids. The experiments proposed will lead to a deeper understanding of the role of ploidy in aberrant cell proliferation.

实验旨在确定酿酒酵母中基因表达受倍性控制的基因表达的机制。 这项工作对人类异常的细胞生长具有影响，因为具有异常细胞控制的肿瘤细胞通常含有异常数量的染色体。 尽管通常视为异常细胞周期控制的结果，但该提案表明多倍性本身可能导致细胞增殖所需的关键分子的异常表达。 基因阵列将用于确定同基因酵母菌菌株中基因转录的倍性控制的分子基础，其倍性菌株从单倍体变化到四倍体。 一组实验旨在识别G1细胞周期蛋白转录在细胞大小和细胞增殖的倍性控制中的作用。 这些研究将确定倍性控制本身是否受到细胞周期调节。 由于多倍体细胞对营养饥饿更为敏感，因此将确定负责异倍体和多倍体生长控制差异的基因。 杂合性在配合类型基因座和染色体配对在多倍体对营养饥饿的反应中的作用将得到确定。 将分析已知的转录控制的基因之一的启动子，以识别对倍形控制响应的顺式作用序列。 另一个屏幕旨在识别介导倍性控制的跨作用基因。 盐耐药性是一种倍性敏感的表型，将用于筛选倍性依赖表型的抑制剂。 另外，将阐明盐敏感性的细胞基础。 第三组实验确定了RIM1转录因子在固定相代谢中的作用。提出了一种已知的青霉素生产真菌调节剂的酵母同系物来控制糖疗法中的固定相代谢。 第四组实验的重点是二平酰胺的作用，这是延伸因子2在细胞调节中的保守后翻译后修饰。 DPH突变体的固定相缺陷在单倍体中的二倍体中再次更为严重。 提出的实验将导致对倍性在异常细胞增殖的作用有更深入的了解。