Understanding the action of molecular motors that remodel packaged DNA

“The DNA in a given human cell is ~two meters long. Yet, this DNA is accommodated in a nucleus of the order of a few microns. This major organizational feat is accomplished by the packaging of DNA in the form of chromatin. The packaging involves wrapping of 1 nm wide double-helical DNA around histone proteins to form 8 nm wide fibers, which are then compacted to form 30 nM wide fibers followed by further folding into higher-order structures. Despite such dense packaging, a human cell responds to extra-cellular signals within minutes by turning on multiple specific genes from within the large mass of compacted and inaccessible DNA.  This ability of a cell is crucial for its normal differentiation, growth and adaptation and relies on the action of specific molecular motors that use the energy of ATP hydrolysis to remodel the packaged DNA. The talk will include an introduction to the general class of questions raised by the regulatory potential of chromatin followed by a description of some recent discoveries in our laboratory that shed light on the mechanisms by which chromatin-remodeling motors work.”