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Nucleic Acids Research 2006 34(1):254-261; doi:10.1093/nar/gkj428
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Published online 9 January 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

Structural and dynamic basis of a supercoiling-responsive DNA element

Sung-Hun Bae, Sang Hoon Yun1, Dawei Sun, Heon M. Lim1 and Byong-Seok Choi*

Department of Chemistry, KAIST 373-1 Guseong-dong Yuseong-gu Daejeon 305-701, Republic of Korea 1Department of Biology, School of Biological Science and Biotechnology, Chungnam National University Daejeon 305-764, Republic of Korea

*To whom correspondence should be addressed. Tel: +82 42 869 2828; Fax: +82 42 869 8120; Email: byongseok.choi{at}kaist.ac.kr

Received July 2, 2005. Revised December 15, 2005. Accepted December 15, 2005.

In both eukaryotes and prokaryotes, negative supercoiling of chromosomal DNA acts locally to regulate a variety of cellular processes, such as transcription, replication, recombination and response to environmental stresses. While studying the interaction between the Hin recombinase and mutated versions of its cognate DNA-binding site, we identified a mutated DNA site that binds Hin only when the DNA is supercoiled. To understand the mechanism of this supercoiling-responsive DNA site, we used NMR spectroscopy and fluorescence resonance energy transfer to determine the solution structures and dynamics of three related DNA oligonucleotides. The supercoiling-responsive DNA site formed a partially unwound and stretched helix and showed significant flexibility and base pair opening kinetics. The single CAG/CTG triplet contained in this DNA sequence displayed the same characteristics as do multiple CAG/CTG repeats, which are associated with several hereditary neuromuscular diseases. It is known that short DNA sequence motifs that have either very high or low bending flexibility occur preferentially at supercoiling-sensitive bacterial and eukaryotic promoters. From our results and these previous data, we propose a model in which supercoiling utilizes the intrinsic flexibility of a short DNA site to switch the local DNA structure from an inefficient conformation for protein binding to an efficient one, or vice versa.

Correspondence may also be addressed to Heon M. Lim. Tel: +82 42 821 6276; Fax: +82 42 822 9690; Email: hmlim{at}cnu.ac.kr


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