During the past few years, it has become increasingly apparent that cells contain a number of proteins that interact with DNA or RNA and thereby alter secondary structures with key roles in the synthesis and function of the polynucleotides. Consequently, malfunctions in the action of these proteins may lead to alterations in the synthesis or function of DNA or RNA, which in turn can lead to a multitude of diseases as diverse as cancer and beta-thalassamia. Conversely, detailed knowledge of the actions of these proteins may provide the basis for more effective treatment or prevention of these diseases. A group of these proteins bind single-stranded DNA or RNA preferentially and stoichiometrically and, thus, lower the melting temperature of the double-stranded polynucleotide. This group of proteins is termed helixdestabilizing protein (HDP). Nearly all of the studies on mammalina HDP have been on purified proteins. Such studies provide an indication of the potential function of the individual protein, but their relevance to physiological processes has not been established. We propose to take one mammalian HDP, HDP-1 and determine its function in living cells. We chose HDP-1 because numerous studies by us and others on the purified protein provide substantial background information and because a remarkable evolutionary conservation evident in the structures of murine and bovine HDP-1 is indicative of a critical function. We propose to use modern biochemical, immunological, and molecular biological techniques to determine if HDP-1 is associated with a particular organelle or intracellular structure, if a correlation exists between the expression of HDP-1 and the physiological state of the cell, if HDP-1 is encoded by a family of closely related genes, and if HDP-1 undergoes post-translational modification. The results obtained from the aforementioned studies will be analyzed an applied to formulate testable hypothesis to aid in the design of experiments to determine the specific function of HDP-1.
