Nucleic Acids Research, 2001, Vol. 29, No. 8 1765-1771
© 2001 Oxford University Press
Substrate-specific inhibition of RecQ helicase
1Department of Molecular Biophysics and Biochemistry and 2Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8024, USA
The RecQ helicases constitute a small but highly conserved helicase family. Proteins in this family are of particular interest because they are critical to maintenance of genomic stability in prokaryotes and eukaryotes. Eukaryotic RecQ helicase family members have been shown to unwind not only DNA duplexes but also DNAs with alternative structures, including structures stabilized by G quartets (G4 DNAs). We report that Escherichia coli RecQ can also unwind G4 DNAs, and that unwinding requires ATP and divalent cation. RecQ helicase is comparably active on duplex and G4 DNA substrates, as measured by direct comparison of protein activity and by competition assays. The porphyrin derivative, N-methyl mesoporphyrin IX (NMM), is a highly specific inhibitor of RecQ unwinding activity on G4 DNA but not duplex DNA: the inhibition constant (Ki) for NMM inhibition of G4 DNA unwinding is 1.7 µM, approximately two orders of magnitude below the Ki for inhibition of duplex DNA unwinding (>100 µM). NMM may therefore prove to be a valuable compound for substrate-specific inhibition of other RecQ family helicases in vitro and in vivo.
* To whom correspondence should be addressed at present address: Departments of Immunology and Biochemistry, University of Washington Medical School, 1959 N.E. Pacific Street, Box 357650, Seattle, WA 98195-7650, USA. Tel: +1 206 221 6876; Fax: +1 206 221 6781; Email: maizels{at}u.washington.edu
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