Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase η

Chembiochem. 2016 Nov 3;17(21):2033-2037. doi: 10.1002/cbic.201600420. Epub 2016 Sep 13.


The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of guanine (C8-dG-ABA). These adducts present a strong block to replicative polymerases but, remarkably, can be bypassed in a largely error-free manner by the human Y-family polymerase η (hPol η). Here, we report the crystal structure of a ternary Pol⋅DNA⋅dCTP complex between a C8-dG-ABA-containing template:primer duplex and hPol η. The complex was captured at the insertion stage and provides crucial insight into the mechanism of error-free bypass of this bulky lesion. Specifically, bypass involves accommodation of the ABA moiety inside a hydrophobic cleft to the side of the enzyme active site and formation of an intra-nucleotide hydrogen bond between the phosphate and ABA amino moiety, allowing the adducted guanine to form a standard Watson-Crick pair with the incoming dCTP.

Keywords: DNA damage; DNA polymerases; X-ray crystallography; environmental carcinogen; lesion bypass; nitrobenzanthrone.

Publication types

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

MeSH terms

  • Benz(a)Anthracenes / chemistry
  • Benz(a)Anthracenes / metabolism*
  • DNA Adducts / chemistry
  • DNA Adducts / metabolism*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / metabolism*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / chemistry
  • Deoxyguanosine / metabolism
  • Humans
  • Models, Molecular
  • Molecular Structure


  • Benz(a)Anthracenes
  • DNA Adducts
  • N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone
  • DNA-Directed DNA Polymerase
  • Rad30 protein
  • Deoxyguanosine