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DNA recognition

Reading the minor groove

Nature volume 391, pages 436–438 (1998)Cite this article

The design of molecules that recognize specific sequences on the DNA double helix would provide new tools to control gene expression and a rational basis for fresh approaches to drug development. Parts of each base pair are exposed in the two distinct ‘grooves’ of DNA, the major and the minor grooves, and the sequence information of the DNA duplex is available for readout from both of them. On page 468 of this issue1, White et al. describe a molecular code for the recognition of the four Watson-Crick base pairs from the minor groove of DNA using hairpin polyamides containing imidazole, pyrrole and 3-hydroxypyrrole rings.

Double-helical DNA can bind different types of ligand which can be classified in two categories: intercalators which insert their aromatic ring between two adjacent base pairs, and groove binders which bind DNA within either groove of the double helix. Intercalators have a limited sequence specificity, because they are interacting only with two base pairs unless they are linked to a groove-recognition element — as exemplified by natural molecules, such as actinomycin; or by synthetic conjugates where an intercalator has been covalently tethered to a major groove ligand, such as an oligonucleotide2, or to a minor groove ligand such as distamycin3. In living organisms, the reading of sequence information on DNA involves binding of proteins to specific control regions of the genes. These proteins exploit all three modes of binding: intercalation or partial insertion of aromatic amino acids, binding of α-helices into the major groove, and binding of loops of polypeptide chains or β-sheets into the minor groove. But no general amino-acid/base-pair code is available yet.

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Figure 1: Differences in DNA base-pair recognition between the major and minor grooves.
Figure 2: Hairpin polyamides.

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  1. the Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U.201 - CNRS URA 481, 43 rue Cuvier, Paris, 75231 Cedex 05, France

    Claude Hélène

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Hélène, C. Reading the minor groove. Nature 391, 436–438 (1998). https://doi.org/10.1038/35026

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