title: Accuracy, lesion bypass, strand displacement and translocation by DNA polymerases.
abstract: The structures of DNA polymerases from different families show common features and significant differences that shed light on the ability of these enzymes to accurately copy DNA and translocate. The structure of a B family DNA polymerase from phage RB69 exhibits an active-site closing conformational change in the fingers domain upon forming a ternary complex with primer template in deoxynucleoside triphosphate. The rotation of the fingers domain alpha-helices by 60 degrees upon dNTP binding is analogous to the changes seen in other families of polymerases. When the 3' terminus is bound to the editing 3' exonuclease active site, the orientation of the DNA helix axis changes by 40 degrees and the thumb domain re-orients with the DNA. Structures of substrate and product complexes of T7 RNA polymerase, a structural homologue of T7 DNA polymerase, show that family polymerases use the rotation conformational change of the fingers domain to translocate down the DNA. The fingers opening rotation that results in translocation is powered by the release of the product pyrophosphate and also enables the Pol I family polymerases to function as a helicase in displacing the downstream non-template strand from the template strand.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520-8114, USA. eatherton@csb.yale.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Steitz
authors.forename: Y Whitney
authors.initials: YW
authors.lastname: Yin
mesh_terms: D001435:Bacteriophages / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D008957:Models, Genetic; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D012318:RNA Polymerase I / Q000378:metabolism*; D014764:Viral Proteins
chemical_list: D014764:Viral Proteins; C062210:bacteriophage T7 RNA polymerase; D012321:DNA-Directed RNA Polymerases; D012318:RNA Polymerase I; D004259:DNA-Directed DNA Polymerase