BIOLOGICAL ROLE OF MOUSE HELIX-DESTABILIZING PROTEIN-1

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.