Selective Incision of the alpha-N-Methyl-Formamidopyrimidine Anomer by Escherichia coli Endonuclease IV.

ABSTRACT: Formamidopyrimidines (Fapy) lesions result from ring opening of the imidazole portion of purines. Fapy lesions can isomerize from the natural beta-anomeric stereochemistry to the alpha-configuration. We have unambiguously demonstrated that the alpha-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 alpha-dG in the same duplex sequence. The alpha- and beta-MeFapy-dG anomers equilibrate to ~21 : 79 ratio over ~3 days. Related studies with a duplex containing the alpha-Fapy-dG lesion derived from aflatoxin B(1) epoxide (alpha-AFB-Fapy-dG) showed only low levels of incision. It is hypothesiz

SUBMITTER: Christov PP 

PROVIDER: S-EPMC2925382 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature