DNA polymerase δ and ζ switch by sharing accessory subunits of DNA polymerase δ

J Biol Chem. 2012 May 18;287(21):17281-17287. doi: 10.1074/jbc.M112.351122. Epub 2012 Mar 30.


Translesion DNA synthesis is an important branch of the DNA damage tolerance pathway that assures genomic integrity of living organisms. The mechanisms of DNA polymerase (Pol) switches during lesion bypass are not known. Here, we show that the C-terminal domain of the Pol ζ catalytic subunit interacts with accessory subunits of replicative DNA Pol δ. We also show that, unlike other members of the human B-family of DNA polymerases, the highly conserved and similar C-terminal domains of Pol δ and Pol ζ contain a [4Fe-4S] cluster coordinated by four cysteines. Amino acid changes in Pol ζ that prevent the assembly of the [4Fe-4S] cluster abrogate Pol ζ function in UV mutagenesis. On the basis of these data, we propose that Pol switches at replication-blocking lesions occur by the exchange of the Pol δ and Pol ζ catalytic subunits on a preassembled complex of accessory proteins retained on DNA during translesion DNA synthesis.

Publication types

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

MeSH terms

  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism*
  • DNA Polymerase III / genetics
  • DNA Polymerase III / metabolism*
  • DNA Replication / physiology*
  • DNA Replication / radiation effects
  • Humans
  • Mutagenesis / radiation effects
  • Poly-ADP-Ribose Binding Proteins
  • Protein Structure, Tertiary
  • Ultraviolet Rays


  • Poly-ADP-Ribose Binding Proteins
  • POLD1 protein, human
  • DNA Polymerase II
  • DNA Polymerase III
  • POLE protein, human