Cellular DNA replicases: components and dynamics at the replication fork

Annu Rev Biochem. 2005:74:283-315. doi: 10.1146/annurev.biochem.73.011303.073859.

Abstract

DNA replicases are multicomponent machines that have evolved clever strategies to perform their function. Although the structure of DNA is elegant in its simplicity, the job of duplicating it is far from simple. At the heart of the replicase machinery is a heteropentameric AAA+ clamp-loading machine that couples ATP hydrolysis to load circular clamp proteins onto DNA. The clamps encircle DNA and hold polymerases to the template for processive action. Clamp-loader and sliding clamp structures have been solved in both prokaryotic and eukaryotic systems. The heteropentameric clamp loaders are circular oligomers, reflecting the circular shape of their respective clamp substrates. Clamps and clamp loaders also function in other DNA metabolic processes, including repair, checkpoint mechanisms, and cell cycle progression. Twin polymerases and clamps coordinate their actions with a clamp loader and yet other proteins to form a replisome machine that advances the replication fork.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • DNA Replication*
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism*
  • Escherichia coli / enzymology
  • Models, Biological
  • Models, Molecular
  • Proliferating Cell Nuclear Antigen / chemistry
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proteins / chemistry
  • Proteins / metabolism

Substances

  • Proliferating Cell Nuclear Antigen
  • Proteins
  • DNA replicase
  • DNA-Directed DNA Polymerase