Nucleic acid condensation and packaging

When DNA is free in solution it acts as a semi-rigid polymer, much like a garden hose would appear if suspended in a swimming pool (but at a much smaller scale). Because DNA is not perfectly flexible, and because the linear length of DNA within any cell or virus is thousands of times greater than the longest dimension of the cell or virus, nature has evolved mechanisms that allow the packaging of DNA at very high density. As a means to understand the properties of DNA that govern the transition of DNA from a fully extended state into a high density particle, our laboratory conducted a series of investigations that have provided fundamental insights regarding the factors that determine the size and morphology of particles that are produced when DNA in condensed in vitro by the addition of multivalent cations, crowding agents and proteins. Our studies have provided insights regarding how DNA is packaged within bacterial viruses (i.e. bacterial phages) and vertebrate sperm cells. Our studies of DNA condensation in the presence of the bacterial proteins HU and IHF, two of the most evolutionarily conserved bacterial proteins, have provided an explanation for how the combination of these proteins and other components of the bacterial cytoplasm allow for the high density packaging of DNA within the bacterial nucleoid. More recent studies of the satellite tobacco mosaic virus genome have provided a model for how the ssRNA of this virus is packaged in an highly symmetric manner as, effectively, dsRNA. 

Representative publications in this area:
S. S. Athavale, J Gossett, J., Bowman, J. C., Hud, N. V., Williams, L. Dean, and Harvey, S. C. (2013) In vitro secondary structure of the genomic RNA of satellite tobacco mosaic virus, PLoS One 8, e54384.

Sarkar, T., Petrov, A. S., Vitko, J. R., Santai, C.T., Harvey, S. C., Mukerji, I. and Hud, N. V. (2009) Integration Host Factor (IHF) Dictates the Structure of Polyamine-DNA Condensates: Implications for the Role of IHF in the Compaction of Bacterial Chromatin, Biochemistry 48, 667-675.

Vilfan, I. D., Conwell, C.C., Sarkar, T. and Hud, N.V. (2006) A Time Study of DNA Condensate Morphology: Implications Regarding the Nucleation, Growth and Equilibrium Populations of Toroids and Rods, Biochemistry 45, 8174-8183.

Conwell, C. C. and Hud, N. V. (2004) Evidence That Both Kinetic and Thermodynamic Factors Govern DNA Toroid Dimensions: Effects of Magnesium(II) on DNA Condensation by Hexammine Cobalt(III), Biochemistry 43, 538-5387.

Vilfan, I. D., Conwell, C. C. and Hud, N. V. (2004) Formation of native-like mammalian sperm cell chromatin with folded bull protamine, J. Biol. Chem. 279, 20088-20095.

N. V. Hud and Downing, K. H. (2001) Cryoelectron microscopy of lambda phage DNA condensates in vitreous ice: The fine structure of DNA toroids, Proc Natl Acad Sci USA 98, 14925-30.