A new proofreading mechanism for lesion bypass by DNA polymerase-λ

EMBO Rep. 2011 Dec 23;13(1):68-74. doi: 10.1038/embor.2011.226.


Replicative DNA polymerases (DNA pols) increase their fidelity by removing misincorporated nucleotides with their 3' → 5' exonuclease activity. Exonuclease activity reduces translesion synthesis (TLS) efficiency and TLS DNA pols lack 3' → 5' exonuclease activity. Here we show that physiological concentrations of pyrophosphate (PP(i)) activate the pyrophosphorolytic activity by DNA pol-λ, allowing the preferential excision of the incorrectly incorporated A opposite a 7,8-dihydro-8-oxoguanine lesion, or T opposite a 6-methyl-guanine, with respect to the correct C. This is the first example of an alternative proofreading mechanism used during TLS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Breaks, Single-Stranded
  • DNA Polymerase beta / metabolism*
  • DNA Repair
  • DNA Replication / physiology
  • Deoxyadenine Nucleotides / metabolism
  • Diphosphates / metabolism
  • Enzyme Activation
  • Guanosine / analogs & derivatives
  • Guanosine / metabolism
  • Humans


  • Deoxyadenine Nucleotides
  • Diphosphates
  • Guanosine
  • 8-hydroxyguanosine
  • diphosphoric acid
  • DNA polymerase beta2
  • DNA Polymerase beta