5-Hydroxypyrimidine deoxynucleoside triphosphates are more efficiently incorporated into DNA by exonuclease-free Klenow fragment than 8-oxopurine deoxynucleoside triphosphates

Nucleic Acids Res. 1994 Sep 25;22(19):3930-5. doi: 10.1093/nar/22.19.3930.

Abstract

Recent studies with 8-oxodeoxyguanosine triphosphate (8-oxodGTP) have suggested that incorporation of oxidized nucleotides from the precursor pool into DNA may have deleterious effects. Here we show that 5-hydroxydeoxycytosine triphosphate (5-OHdCTP) and 5-hydroxydeoxyuridine triphosphate (5-OHdUTP) are more efficient substrates than 8-oxodGTP for Escherichia coli DNA polymerase I Klenow fragment lacking proofreading activity, while 8-oxodeoxyadenosine triphosphate (8-oxodGTP, 5-OHdCTP can mispair with dA in DNA but with lower efficiency. Since the 5-hydroxypyrimidines are present in normal and oxidized cellular DNA in amounts similar to the 8-oxopurines, these data suggest that enzymatic mechanisms might exist for removing them from the DNA precursor pools.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA / biosynthesis*
  • DNA Polymerase I / metabolism*
  • Deoxyadenine Nucleotides / metabolism
  • Deoxycytosine Nucleotides / chemical synthesis
  • Deoxycytosine Nucleotides / metabolism*
  • Deoxyguanine Nucleotides / chemical synthesis
  • Deoxyguanine Nucleotides / metabolism*
  • Deoxyuracil Nucleotides / chemical synthesis
  • Deoxyuracil Nucleotides / metabolism*
  • Kinetics
  • Molecular Sequence Data
  • Templates, Genetic

Substances

  • 2'-deoxy-5-hydroxycytosine triphosphate
  • 8-oxodeoxyadenosine triphosphate
  • Deoxyadenine Nucleotides
  • Deoxycytosine Nucleotides
  • Deoxyguanine Nucleotides
  • Deoxyuracil Nucleotides
  • 8-oxodeoxyguanosine triphosphate
  • 2'-deoxy-5-hydroxyuridine triphosphate
  • DNA
  • DNA Polymerase I