Understanding the structural basis of the replisome function, piece by piece

BIOL 4

Thomas A Steitz, eatherton@mail.csb.yale.edu, Molecular Biophysics and Biochemistry, Yale University, 266 whitney ave, New Haven, CT 06510
Genomic DNA is copied by a macromolecular machine called the replisome, which in bacteria is comprised of the replicating DNA polymerase III (DNAP III), the sliding clamp and the primasome consisting of DnaB helicase and primase. The structure of eubacterial DNAP III (1) is not related to that of the replicating polymerase from eukaryotes raising the question of what replicated the DNA of the last common ancestor (a ribozyme?). The structure of the DNAP III ternary substrate complex shows many domain rearrangements including one that is repositioned to bind sliding clamp. The structure of the hexameric DnaB helicase complexed with three helicase binding domains of primase exhibits 3-fold rather than 6-fold symmetry and a central channel large enough to accommodate duplex DNA. The structure of the helicase-primase complex is in progress, but substrate complexes remain elusive.

1. Bailey, S., Wing, R.A. and Steitz, T.A. Cell 126: 893-904 (2006).