MINORITY PREDOCTORAL FELLOWSHIP

SPT3和MOT1是两个酵母基因，它们与TATA结合蛋白(TBP)的功能有关，TBP是正常转录所必需的。它们被认为是功能相关的，因为spt3mot1双重突变体是不可行的。在对这种致命性的高拷贝抑制物的筛选中发现了mot3，这表明mot3蛋白对正常的TBP功能也是重要的。由于遗传分析表明mot3对生长不是必需的，但mot3的功能丧失会在体内造成轻微的转录缺陷，因此mot3在细胞中可能是功能冗余的。这项建议的具体目的是(1)通过筛选仅当与mot3突变结合时才导致丧失生存能力或强突变表型的突变，来研究mot3可能的功能冗余；(2)通过双杂交筛选来鉴定可能与mot3物理上相互作用的蛋白质。这些研究mot3的互补方法可能会识别已知的对转录重要或必不可少的因素和/或尚未研究的基因。由于转录缺陷与许多人类疾病有关，如癌症，而且转录过程在真核生物中高度保守，在这些研究过程中获得的结果将与人类健康相关。

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.