MINORITY PREDOCTORAL FELLOWSHIP

少数族裔博士前奖学金

• 批准号: 6329592
• 负责人: CINTIA Fabiana HONGAY
• 金额: $ 2.04万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-11-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6329592
• 关键词: DNA binding protein; fungal genetics; gene expression; gene mutation; transcription factor; yeast two hybrid system

SPT3 and MOT1 are two yeast genes implicated in the function of the TATA-binding protein (TBP) which are required for normal transcription. They are believed to be functionally related since an spt3 mot1 double mutant is inviable. MOT3 was identified in a screen for high-copy suppressors of this lethality, suggesting that the Mot3 protein is also important for normal TBP function. As genetic analysis demonstrated that Mot3 is not essential for growth, but that loss of function of Mot3 causes mild transcriptional defects in vivo, it is possible that Mot3 is functionally redundant in the cell. The specific aims of this proposal are (1) to investigate the possible functional redundancy of MOT3 by screening for mutations that cause either inviability or strong mutant phenotypes only when in combination with a mot3 mutation and (2) to identify proteins that may physically interact with Mot3 by a two-hybrid screen. These complementary approaches to the study of Mot3 will likely identify factors already known to be important or essential for transcription and/or yet unstudied genes. As transcriptional defects have been implicated in many human disorders such as cancer, and since the transcription process is highly conserved among eukaryotes, results obtained during the course of these studies will be relevant to human health.

SPT3和MOT1是酵母中与tata结合蛋白（TBP）功能有关的两个基因，是正常转录所必需的。它们被认为是功能相关的，因为spt3 mot1双突变体是不可存活的。在筛选这种致死率的高拷贝抑制因子时发现了MOT3，这表明MOT3蛋白对正常的TBP功能也很重要。遗传分析表明，mo3不是生长所必需的，但mo3的功能丧失会在体内引起轻微的转录缺陷，因此，mo3在细胞中可能是功能冗余的。本提案的具体目的是：(1)通过筛选仅在与MOT3突变结合时导致无活力或强突变表型的突变来研究MOT3可能的功能冗余；(2)通过双杂交筛选鉴定可能与MOT3物理相互作用的蛋白质。这些对Mot3研究的补充方法可能会确定已知的对转录和/或尚未研究的基因重要或必需的因素。由于转录缺陷与许多人类疾病（如癌症）有关，并且由于转录过程在真核生物中高度保守，因此在这些研究过程中获得的结果将与人类健康有关。