Published online 27 August 2004
Nucleic Acids Research, Vol. 32 No. 15 © Oxford University Press 2004; all rights reserved
Phosphorylation at 5' end of guanosine stretches inhibits dimerization of G-quadruplexes and formation of a G-quadruplex interferes with the enzymatic activities of DNA enzymes
1 Gene Function Research Center and 2 iGENE Therapeutics, Inc., National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan, 3 Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Tokyo 113-8656, Japan and 4 Department of Chemistry, University of Tsukuba, Tsukuba Science City 305-8571, Japan
* To whom correspondence should be addressed at Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Tokyo 113-8656, Japan. Tel: +81 3 5841 8828 or +81 29 8613015; Fax: +81 29 861 3019 or +81 3 5841 8828; Email: taira{at}chembio.t.u-tokyo.ac.jp
Correspondence may also be addressed to Yasuomi Takagi. Tel: +81 29 860 3203; Fax: +81 29 860 3205; Email: y-takagi{at}igene-therapeutics.co.jp
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors
Received February 2, 2004; Revised April 30, 2004; Accepted July 26, 2004
During an analysis of DNA enzymes by gel electrophoresis, we found that some DNA enzymes can adopt more than one conformation. The DNA enzyme Dz31 that formed more than one conformer contained a stretch of G residues. Further investigations, involving kinetic analysis and measurements of circular dichroism, indicated that this DNA enzyme and its derivatives formed G-quadruplexes. Moreover, we found that some derivative oligomers were capable of forming dimeric G-quadruplexes. We also compared the catalytic activities of Dz31 and its mutant derivatives. The present findings suggest that DNA enzymes with five or more continuous G residues are less favorable than those without G5 in the association step in the enzymatic reaction and, thus, the choice of targets that contain a continuous stretch of C residues downstream of the cleavage site should be avoided. In addition, we found that negative charge–charge repulsion disrupted the dimerization of G-quadruplexes when a phosphate group was added directly to the 5'-terminal G of oligomers with continuous guanosine residues. In the case of 5'-phosphorylated G5CTA, direct attachment of a phosphate group to the continuous G5 sequence inhibited dimerization of G-quadruplexes, at least during electrophoresis on a denaturing gel.
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