Journal of Nucleic Acids (Jan 2010)

Selective Incision of the α-N5-Methyl-Formamidopyrimidine Anomer by Escherichia coli Endonuclease IV

  • Plamen P. Christov,
  • Surajit Banerjee,
  • Michael P. Stone,
  • Carmelo J. Rizzo

DOI
https://doi.org/10.4061/2010/850234
Journal volume & issue
Vol. 2010

Abstract

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Formamidopyrimidines (Fapy) lesions result from ring opening of the imidazole portion of purines. Fapy lesions can isomerize from the natural β-anomeric stereochemistry to the α-configuration. We have unambiguously demonstrated that the α-methyl-Fapy-dG (MeFapy-dG) lesion is a substrate for Escherichia coli Endonuclease IV (Endo IV). Treatment of a MeFapy-dG-containing 24 mer duplex with Endo IV resulted in 36–40% incision. The catalytic efficiency of the incision was comparable to that of α-dG in the same duplex sequence. The α- and β-MeFapy-dG anomers equilibrate to ~21 : 79 ratio over ~3 days. Related studies with a duplex containing the α-Fapy-dG lesion derived from aflatoxin B1 epoxide (α-AFB-Fapy-dG) showed only low levels of incision. It is hypothesized that the steric bulk of the aflatoxin moiety interferes with the binding of the substrate to Endo IV and the incision chemistry.