Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator
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.
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).
Published - PIEpnas07.pdf