Translesion synthesis past acrolein-derived DNA adduct, gamma -hydroxypropanodeoxyguanosine, by yeast and human DNA polymerase eta

J Biol Chem. 2003 Jan 10;278(2):784-90. doi: 10.1074/jbc.M207774200. Epub 2002 Oct 24.


gamma-Hydroxy-1,N(2)-propano-2'deoxyguanosine (gamma-HOPdG) is a major deoxyguanosine adduct derived from acrolein, a known mutagen. In vitro, this adduct has previously been shown to pose a severe block to translesion synthesis by a number of polymerases (pol). Here we show that both yeast and human pol eta can incorporate a C opposite gamma-HOPdG at approximately 190- and approximately 100-fold lower efficiency relative to the control deoxyguanosine and extend from a C paired with the adduct at approximately 8- and approximately 19-fold lower efficiency. Although DNA synthesis past gamma-HOPdG by yeast pol eta was relatively accurate, the human enzyme misincorporated nucleotides opposite the lesion with frequencies of approximately 10(-1) to 10(-2). Because gamma-HOPdG can adopt both ring closed and ring opened conformations, comparative replicative bypass studies were also performed with two model adducts, propanodeoxyguanosine and reduced gamma-HOPdG. For both yeast and human pol eta, the ring open reduced gamma-HOPdG adduct was less blocking than gamma-HOPdG, whereas the ring closed propanodeoxyguanosine adduct was a very strong block. Replication of DNAs containing gamma-HOPdG in wild type and xeroderma pigmentosum variant cells revealed a somewhat decreased mutation frequency in xeroderma pigmentosum variant cells. Collectively, the data suggest that pol eta might potentially contribute to both error-free and mutagenic bypass of gamma-HOPdG.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acrolein / metabolism
  • Acrolein / toxicity*
  • DNA Adducts / chemistry
  • DNA Adducts / metabolism*
  • DNA Polymerase iota
  • DNA Replication*
  • DNA-Directed DNA Polymerase / physiology*
  • Deoxyguanosine / metabolism*
  • Humans
  • Saccharomyces cerevisiae Proteins / physiology*


  • DNA Adducts
  • Saccharomyces cerevisiae Proteins
  • Acrolein
  • DNA-Directed DNA Polymerase
  • Deoxyguanosine
  • DNA Polymerase iota
  • POLI protein, human