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The heptad repeat in the largest subunit of RNA polymerase II binds by intercalating into DNA

Nature volume 344, pages 562–565 (1990)Cite this article

Abstract

A TANDEM repeat of the sequence Ser-Pro-Thr-Ser-Pro-Ser-Tyr has been found at the C terminus in the largest subunit of RNA polymerase II (refs 1–5) with, for example, 26 units in yeast2 and 52 in mammals3,5. By removal of this 'tail', it has been shown that 11–23 units are necessary for the normal functioning of the poly-merase4,5. The functional role of the repeat is however, unclear, although it has been proposed that it binds to transcription factors6. As discussed in an earlier paper7, the repeat unit contains two Ser-Pro sequences which seem to be related to a DNA-binding unit found in histones, Ser-Pro-Lys-Lys8, and to the Ser-Pro-X-X motif which is often found in gene regulatory proteins and which, it has been proposed, is also a DNA-binding unit7. Here, I show that the repeat does indeed bind DNA and present evidence that it does so by the intercalation of tyrosine residues. These experi-ments involved synthetic peptides containing one or two repeat units. As the sequence Ser-Pro-X-X (where X represents any amino acid) has a strong tendency to assume a special β-turn7, a model of the unit composed of two such β-turns was made and compared with the structure of the drug Triostin A which is known to intercalate into DNA9,10. Two tyrosine side chains of the repeat overlap well with two quinoxaline rings of the drug and therefore, the model can provide a good explanation of the experimental results.

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  1. Masashi Suzuki

    Present address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

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  1. Laboratory of Neurochemistry, Division of Molecular Physiology, National Institute for Physiological Sciences, Okazaki, 444, Japan

    Masashi Suzuki

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  1. Masashi Suzuki
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Suzuki, M. The heptad repeat in the largest subunit of RNA polymerase II binds by intercalating into DNA. Nature 344, 562–565 (1990). https://doi.org/10.1038/344562a0

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