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Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator

Pierre, Valerie C. and Kaiser, Jens T. and Barton, Jacqueline K. (2007) Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator. Proceedings of the National Academy of Sciences of the United States of America, 104 (2). pp. 429-434. ISSN 0027-8424. PMCID PMC1766401. http://resolver.caltech.edu/CaltechAUTHORS:PIEpnas07

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Abstract

We report the 1.1-Å resolution crystal structure of a bulky rhodium complex bound to two different DNA sites, mismatched and matched in the oligonucleotide 5'-(dCGGAAATTCCCG)2-3'. At the AC mismatch site, the structure reveals ligand insertion from the minor groove with ejection of both mismatched bases and elucidates how destabilized mispairs in DNA may be recognized. This unique binding mode contrasts with major groove intercalation, observed at a matched site, where doubling of the base pair rise accommodates stacking of the intercalator. Mass spectral analysis reveals different photocleavage products associated with the two binding modes in the crystal, with only products characteristic of mismatch binding in solution. This structure, illustrating two clearly distinct binding modes for a molecule with DNA, provides a rationale for the interrogation and detection of mismatches.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766401/PubMed CentralArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:Copyright © 2007 by the National Academy of Sciences. Contributed by Jacqueline K. Barton, November 15, 2006 (received for review November 7, 2006). Published online before print December 28, 2006, 10.1073/pnas.0610170104 We thank M. Day for assistance in structure refinement, D.C. Rees for valuable discussions, and B.M. Zeglis for assistance in the gel electrophoresis experiments. We acknowledge support from the National Institutes of Health (Grant GM33309) and the Gordon and Betty Moore Foundation to the Caltech Molecular Observatory. The rotation camera facility at Stanford Synchrotron Radiation Laboratory is supported by the U.S. Department of Energy and National Institutes of Health. Author contributions: V.C.P. and J.K.B. designed research; V.C.P. and J.T.K. performed research; and V.C.P. and J.K.B. wrote the paper. The authors declare no conflict of interest. Data deposition: The coordinates described in this paper have been deposited in the Nucleic Acid Database, Department of Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, http://ndbserver.rutgers.edu (NDB structure ID code DD0088; PDB ID 201I).
Funders:
Funding AgencyGrant Number
NIHGM33309
Gordon and Betty Moore FoundationUNSPECIFIED
Department of Energy (DOE)UNSPECIFIED
Subject Keywords:DNA recognition; metallointercalator; mismatch detection
PubMed Central ID:PMC1766401
Record Number:CaltechAUTHORS:PIEpnas07
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:PIEpnas07
Alternative URL:http://dx.doi.org/10.1073/pnas.0610170104
Official Citation:Valérie C. Pierre, Jens T. Kaiser, and Jacqueline K. Barton Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator PNAS 2007 104 (2) 429-434; published ahead of print December 28, 2006, doi:10.1073/pnas.0610170104
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8435
Collection:CaltechAUTHORS
Deposited By: Lindsay Cleary
Deposited On:13 Aug 2007
Last Modified:26 Jan 2016 02:10

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