Structural basis of recruitment of DNA polymerase ζ by interaction between REV1 and REV7 proteins

J Biol Chem. 2012 Sep 28;287(40):33847-52. doi: 10.1074/jbc.M112.396838. Epub 2012 Aug 2.


REV1, REV3, and REV7 are pivotal proteins in translesion DNA synthesis, which allows DNA synthesis even in the presence of DNA damage. REV1 and REV3 are error-prone DNA polymerases and function as inserter and extender polymerases in this process, respectively. REV7 interacts with both REV1 and REV3, acting as an adaptor that functionally links the two, although the structural basis of this collaboration remains unclear. Here, we show the crystal structure of the ternary complex, composed of the C-terminal domain of human REV1, REV7, and a REV3 fragment. The REV1 C-terminal domain adopts a four-helix bundle that interacts with REV7. A linker region between helices 2 and 3, which is conserved among mammals, interacts with the β-sheet of REV7. Remarkably, the REV7-binding interface is distinct from the binding site of DNA polymerase η or κ. Thus, the REV1 C-terminal domain might facilitate polymerase switching by providing a scaffold for both inserter and extender polymerases to bind. Our structure reveals the basis of DNA polymerase ζ (a complex of REV3 and REV7) recruitment to the stalled replication fork and provides insight into the mechanism of polymerase switching.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • DNA Repair
  • DNA Replication
  • DNA-Binding Proteins / chemistry
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / physiology
  • Humans
  • Mad2 Proteins
  • Models, Molecular
  • Molecular Conformation
  • Neoplasms / drug therapy
  • Nuclear Proteins / chemistry*
  • Nucleotidyltransferases / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*


  • DNA-Binding Proteins
  • MAD2L2 protein, human
  • Mad2 Proteins
  • Nuclear Proteins
  • Proteins
  • DNA polymerase zeta
  • Nucleotidyltransferases
  • REV1 protein, human
  • DNA-Directed DNA Polymerase
  • REV3L protein, human

Associated data

  • PDB/3VU7