Motors, switches, and contacts in the replisome

Annu Rev Biochem. 2009:78:205-43. doi: 10.1146/annurev.biochem.78.072407.103248.

Abstract

Replisomes are the protein assemblies that replicate DNA. They function as molecular motors to catalyze template-mediated polymerization of nucleotides, unwinding of DNA, the synthesis of RNA primers, and the assembly of proteins on DNA. The replisome of bacteriophage T7 contains a minimum of proteins, thus facilitating its study. This review describes the molecular motors and coordination of their activities, with emphasis on the T7 replisome. Nucleotide selection, movement of the polymerase, binding of the processivity factor, unwinding of DNA, and RNA primer synthesis all require conformational changes and protein contacts. Lagging-strand synthesis is mediated via a replication loop whose formation and resolution is dictated by switches to yield Okazaki fragments of discrete size. Both strands are synthesized at identical rates, controlled by a molecular brake that halts leading-strand synthesis during primer synthesis. The helicase serves as a reservoir for polymerases that can initiate DNA synthesis at the replication fork. We comment on the differences in other systems where applicable.

Publication types

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

MeSH terms

  • Bacteriophage T4 / genetics
  • Bacteriophage T4 / metabolism
  • Bacteriophage T7 / chemistry
  • Bacteriophage T7 / genetics
  • Bacteriophage T7 / metabolism*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Replication*
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli / virology

Substances

  • DNA, Viral
  • DNA-Directed DNA Polymerase
  • DNA Helicases