DNA Flexibility in Cells

Researchers in the Maher lab at Mayo Clinic are interested in understanding how the locally stiff DNA double helix is managed within cells so that it can be folded, bent and looped during packaging and gene expression. In ongoing fundamental research projects, Jim Maher's team is studying whether electrostatic (charge-charge) interactions are sufficient to explain how some proteins induce DNA to bend. The team is curious whether neutralization of negative charges along one face of DNA can cause the molecule to bend by collapse.

In related studies, lab members are exploring the mechanisms of proteins that cause DNA to become more flexible. One focus is on the HMGB proteins that bind DNA without sequence preference. Maher and colleagues wish to better understand the mechanism of these proteins and how they assist DNA looping in living cells.

An important model system in the lab is natural regulation of the E. coli lactose operon by DNA looping. DNA appears to be more flexible in living bacteria than expected from experiments with isolated DNA molecules. The Maher lab is studying hypotheses to explain this surprising result.

Using insights gained from studies of DNA looping in bacteria, the Maher lab is engineering new DNA looping proteins for artificial control of gene expression in prokaryotic and eukaryotic cells.