January 23, 2013

New view of DNA processing ‘hub’

Structural studies reveal a new framework for understanding a central player in DNA processing.

Faithful replication and propagation of our genome requires the action of molecular machines assembled from proteins that process the DNA. At the center of these various machines lies replication protein A (RPA), the central “hub” that serves as the anchor to the DNA and orchestrates the comings and goings of the proteins that act on it.


Walter Chazin, Ph.D., Chancellor’s Chair in Medicine, and colleagues have now combined small-angle X-ray and neutron scattering with dynamic molecular modeling to determine how the structure of RPA responds as it engages DNA. They report in Nucleic Acids Research that, in contrast with previous models, RPA becomes progressively more compact and less dynamic as it interacts with ssDNA. They also demonstrated that RPA undergoes two transitions as it binds ssDNA, not three as previously believed.

The results provide a new framework for understanding how RPA functions in DNA processing machines and should be broadly applicable to investigations of the action of multi-protein machinery. 

This research was supported by grants from the National Institutes of Health (GM065484, GM046312, CA092584).