The broad long term goals of this proposal are to study novel factors involved in the 3' end processing of histone pre-mRNA and how these factors communicate with the cell-cycle regulatory machinery. The project will be carried out in two different yet complementary model systems: Drosophila and mammalian cultured cells. Novel components required for processing of Drosophila histone pre-mRNA have recently been identified using a genome-wide dsRNA screen and this proposal is aimed at understanding the function that these new proteins play both in flies and mammals. Moreover, a novel function for a known component of this process has been recently identified as playing an essential role in the cell cycle progression. This proposal will also study the nature of this novel function and how this ties into histone pre-mRNA processing. The long term goal of the principle investigator of this research plan is to run an independent research project in a tenure-track University faculty position. This research program would involve the training of graduate students and postdoctoral fellows as well as the standard teaching requirements associated with such a position. This application is vital to the development of this career path as it includes further training from my mentor as well as a continuation of a fruitful collaborative effort with another faculty member at the University of North Carolina. Understanding the mechanisms regulating the biosynthesis of histones is essential to understand the pathology associated with Cancer. Many common chemotherapeutic anti-cancer therapies aim at inhibiting DMA synthesis. Inhibition of histone synthesis should have an equally benefical result, thus having a detailed knowledge of this pathway will increase the repetoire of drugs capable of treating this disease.
