• DNA self-assembly by protamines in vitro and in vivo.

In nature, DNA exists primarily in a highly condensed state. DNA packaging in the cell is typically protein mediated using, for example, histones (in eukaryotic nuclei) or protamines (in sperm cells). The scale of this compaction is immense. For a typcial human chromosome consisting of a single DNA approx. 5 cm in length, every cell thus has almost 2 meters of DNA compacted within its roughly 10 µm size. We work to address fundamental biophysical questions of DNA condensation by integrating x-ray scattering and osmotic stress experiments to investigate how cations mediate DNA-DNA intermolecular forces while extending from in vitro to in vivo packaging, such as protamine mediated condensation in mammalian sperm cells. Our long-term goal is to identify the biochemistry that underlies DNA packaging and mispackaging and understand the interrelationship to DNA damage, disease, and reproductive health.

Figure 1. Toroidal DNA packaging in vitro by (A) cobalt hexamine and (B) protamine. (C) Photomicrograph (Nomarski differential interference contrast) of sperm bound to the Zona pellucida of an ovulated mouse egg.

Pictures reprinted from

A) Hud, N.V. and Downing, K.H. (2001) Cryoelectron microscopy of lambda phage DNA condensates in vitreous ice: The fine structure of DNA toroids. Proceedings of the National Academy of Sciences of the United States of America, 98, 14925-14930.

B) Balhorn, R. (2007) The protamine family of sperm nuclear proteins. Genome Biology, 8, 227.

C) Wassarman, P.M., Jovine, L., Qi, H., Williams, Z., Darie, C. and Litscher, E.S. (2005) Recent aspects of mammalian fertilization research. Molecular and Cellular Endocrinology, 234, 95-103.