Molecular events during translocation and proofreading extracted from 200 static structures of DNA polymerase

Nucleic Acids Res. 2016 Sep 6;44(15):7457-74. doi: 10.1093/nar/gkw555. Epub 2016 Jun 20.

Abstract

DNA polymerases in family B are workhorses of DNA replication that carry out the bulk of the job at a high speed with high accuracy. A polymerase in this family relies on a built-in exonuclease for proofreading. It has not been observed at the atomic resolution how the polymerase advances one nucleotide space on the DNA template strand after a correct nucleotide is incorporated, that is, a process known as translocation. It is even more puzzling how translocation is avoided after the primer strand is excised by the exonuclease and returned back to the polymerase active site once an error occurs. The structural events along the bifurcate pathways of translocation and proofreading have been unwittingly captured by hundreds of structures in Protein Data Bank. This study analyzes all available structures of a representative member in family B and reveals the orchestrated event sequence during translocation and proofreading.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Catalytic Domain
  • DNA / biosynthesis
  • DNA / chemistry
  • DNA / metabolism
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Databases, Protein
  • Models, Molecular
  • Mutation
  • Templates, Genetic

Substances

  • DNA
  • DNA-Directed DNA Polymerase