Predoctoral Fellowship for Disabled Students

描述（由申请人提供）：核糖体生物发生是最基本的细胞过程之一，因为没有核糖体细胞就会停止生长。在后生动物细胞中，核糖体的生物发生受细胞周期调控，因为核糖体的转录和加工在有丝分裂期间停止（Dundr, 1998; Sirri, 2000）。目前，人们对核糖体生物发生与细胞周期之间的联系知之甚少。使用酵母作为模型系统，首先我计划确定核糖体生物发生是否受细胞周期调节。其次，我将确定nanl /Utpl 7是否可以在这两个过程之间提供监管链接。Nanl/Utpl7， Net 1相关核蛋白，最初被纯化为RENT复合体的一个组成部分，RENT复合体是细胞核沉默和末期的调节剂，对有丝分裂的退出很重要（Shou, 1999）。它也被纯化为新纯化的SSU加工体的一个组成部分，在那里它影响18S核糖体亚基的加工（Dragon等人，提交）。因此，Nanl/Utpl7可能提供了这两个进程之间的链接。最后，我将确定是否有生长和分裂所需的临界数量的核糖体。在研究这两个基本过程之间的联系时，我将能够理解异常细胞生长和核糖体合成是如何直接联系在一起的，例如在人类癌症的情况下。

DESCRIPTION (provided by applicant): Ribosome biogenesis is one of the most fundamental of cellular processes because without ribosomes cells cease growing. In metazoan cells, ribosome biogenesis is cell cycle regulated, as both transcription and processing of ribosomes ceases during mitosis (Dundr, 1998; Sirri, 2000). Currently, little else known about the connection between ribosome biogenesis and the cell cycle. Using yeast as a model system, first I plan to determine whether ribosome biogenesis is cell cycle regulated. Second, I will determine whetheNanl/Utpl 7 may provide a regulatory link between these two processes. Nanl/Utpl7, Net 1 associated nucleolarprotein, was originally purified as a component of the RENT complex, Regulator of Nuclealor Silencing and Telophase, which is important for mitotic exit (Shou, 1999). It has also been purified as a component of the newly purified SSU processome, where it affects processing of 18S ribosomal subunits (Dragon et al., Submitted). Therefore, Nanl/Utpl7 may provide a link between these two processes. Finally, I will determine whether there are a critical number of ribosomes needed for growth and division. In studying the link between these two fundamental processes, I will be able to understand how abnormal cell growth and ribosome synthesis are directly connected, such as in the case of human cancers.