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  Inducing and modulating anisotropic DNA bends by pseudocomplementary peptide nucleic acids

Kuhn, H., Cherny, D. I., Demidov, V. V., & Frank-Kamenetskii, M. D. (2004). Inducing and modulating anisotropic DNA bends by pseudocomplementary peptide nucleic acids. Proceedings of the National Academy of Sciences of the United States of America, 101(20): doi:10.1073/pnas.0308756101, pp. 7548-7553. Retrieved from http://www.pnas.org/content/101/20/7548.full.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-ED4F-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-7F0E-A
Genre: Journal Article

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Kuhn, H.1, Author              
Cherny, D. I.2, Author              
Demidov, V. V., Author
Frank-Kamenetskii, M. D., Author
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1Abteilung Molekularer Systemaufbau, MPI for biophysical chemistry, Max Planck Society, ou_578552              
2Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society, ou_578628              

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 Abstract: DNA bending is significant for various DNA functions in the cell. Here, we demonstrate that pseudocomplementary peptide nucleic acids (pcPNAs) represent a class of versatile, sequence-specific DNA-bending agents. The occurrence of anisotropic DNA bends induced by pcPNAs is shown by gel electrophoretic phasing analysis. The magnitude of DNA bending is determined by circular permutation assay and by electron microscopy, with good agreement of calculated mean values between both methods. Binding of a pair of 10-meric pcPNAs to its target DNA sequence results in moderate DNA bending with a mean value of 40–45°, while binding of one self-pc 8-mer PNA to target DNA yields a somewhat larger average value of the induced DNA bend. Both bends are found to be in phase when the pcPNA target sites are separated by distances of half-integer numbers of helical turns of regular duplex DNA, resulting in an enhanced DNA bend with an average value in the range of 80–90°. The occurrence of such a sharp bend within the DNA double helix is confirmed and exploited through efficient formation of 170-bp-long DNA minicircles by means of dimerization of two bent DNA fragments. The pcPNAs offer two main advantages over previously designed classes of nonnatural DNAbending agents: they have very mild sequence limitations while targeting duplex DNA and they can easily be designed for a chosen target sequence, because their binding obeys the principle of complementarity. We conclude that pcPNAs are promising tools for inducing bends in DNA at virtually any chosen site.

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Language(s): eng - English
 Dates: 2004-05-242004-05-18
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Pages: - Volume / Issue: 101 (20) Sequence Number: doi:10.1073/pnas.0308756101 Start / End Page: 7548 - 7553 Identifier: -