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Topological constraints in nucleic acid hybridization kinetics

Bois, Justin S. and Venkataraman, Suvir and Choi, Harry M. T. and Spakowitz, Andrew J. and Wang, Zhen-Gang and Pierce, Niles A. (2005) Topological constraints in nucleic acid hybridization kinetics. Nucleic Acids Research, 33 (13). pp. 4090-4095. ISSN 0305-1048. PMCID PMC1180668.

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A theoretical examination of kinetic mechanisms for forming knots and links in nucleic acid structures suggests that molecules involving base pairs between loops are likely to become topologically trapped in persistent frustrated states through the mechanism of ‘helix-driven wrapping’. Augmentation of the state space to include both secondary structure and topology in describing the free energy landscape illustrates the potential for topological effects to influence the kinetics and function of nucleic acid strands. An experimental study of metastable complementary ‘kissing hairpins’ demonstrates that the topological constraint of zero linking number between the loops effectively prevents conversion to the minimum free energy helical state. Introduction of short catalyst strands that break the topological constraint causes rapid conversion to full duplex.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Bois, Justin S.0000-0001-7137-8746
Choi, Harry M. T.0000-0002-1530-0773
Spakowitz, Andrew J.0000-0002-0585-1942
Wang, Zhen-Gang0000-0002-3361-6114
Pierce, Niles A.0000-0003-2367-4406
Additional Information:© The Author 2005. Published by Oxford University Press. 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 Received April 24, 2005. Revised May 17, 2005. Accepted July 4, 2005. We are grateful to J. Bloom for performing the initial experimental studies on the kissing hairpin system, to G.Seelig for discussions on hybridization catalysts, and to H. Isambert for discussions on the disparity in chain diffusion and helix nucleation time scales. This work was supported by the Charles Lee Powell Foundation (N.A.P.), the Ralph M. Parsons Foundation (N.A.P.), the NSF CAREER program (N.A.P.) and the Caltech Center for Biological Circuit Design (S.V.). Funding to pay the Open Access publication charges for this article was provided by NSF grant CCF-0448835. Conflict of interest statement. None declared. The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
Funding AgencyGrant Number
Charles Lee Powell FoundationUNSPECIFIED
Ralph M. Parsons FoundationUNSPECIFIED
Caltech Center for Biological Circuit DesignUNSPECIFIED
Issue or Number:13
PubMed Central ID:PMC1180668
Record Number:CaltechAUTHORS:BOInar05
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:743
Deposited By: Archive Administrator
Deposited On:23 Sep 2005
Last Modified:09 Mar 2020 13:19

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