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The extended and eccentric E-DNA structure induced by cytosine methylation or bromination

Nature Structural Biology volume 7, pages 758–761 (2000)Cite this article

Abstract

Cytosine methylation or bromination of the DNA sequence d(GGCGCC)2 is shown here to induce a novel extended and eccentric double helix, which we call E-DNA. Like B-DNA, E-DNA has a long helical rise and bases perpendicular to the helix axis. However, the 3′-endo sugar conformation gives the characteristic deep major groove and shallow minor groove of A-DNA. Also, if allowed to crystallize for a period of time longer than that yielding E-DNA, the methylated sequence forms standard A-DNA, suggesting that E-DNA is a kinetically trapped intermediate in the transition to A-DNA. Thus, the structures presented here chart a crystallographic pathway from B-DNA to A-DNA through the E-DNA intermediate in a single sequence. The E-DNA surface is highly accessible to solvent, with waters in the major groove sitting on exposed faces of the stacked nucleotides. We suggest that the geometry of the waters and the stacked base pairs would promote the spontaneous deamination of 5-methylcytosine in the transition mutation of dm5C-dG to dT-dA base pairs.

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Figure 1: Comparing E-DNA with B-DNA and A-DNA.
Figure 2: Electron density maps showing stereo views looking into the major grooves of the B-, E-, and A-DNA structures.
Figure 3: Waters in the CpG dinucleotides of B-DNA and E-DNA.

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Acknowledgements

We thank B.H.M. Mooers and the P.A. Karplus laboratory for helpful discussion, and K.E. van Holde, C.K. Mathews, and W.C. Johnson, Jr. for reading this manuscript. This work was supported by the National Science Foundation, the Oregon American Cancer Society, and the Environmental Heath Science Center at OSU. X-ray facilities were funded in part by the M.J. Murdock Charitable Trust.

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  1. Department of Biochemistry and Biophysics, ALS 2011, Oregon State University, Corvallis, 97331-7305, Oregon, USA

    Jeffrey M. Vargason, Brandt F. Eichman & P. Shing Ho

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  1. Jeffrey M. Vargason
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Correspondence to P. Shing Ho.

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Vargason, J., Eichman, B. & Ho, P. The extended and eccentric E-DNA structure induced by cytosine methylation or bromination. Nat Struct Mol Biol 7, 758–761 (2000). https://doi.org/10.1038/78985

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