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Wiley, FEBS Journal, 20(277), p. 4254-4264, 2010

DOI: 10.1111/j.1742-4658.2010.07814.x

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A novel G-quadruplex motif modulates promoter activity of human thymidine kinase 1: G-quadruplex motif in human thymidine kinase 1

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

G-quadruplex motifs constitute unusual DNA secondary structures formed by stacking of planar hydrogen-bonded G-tetrads. Recent genome-wide bioinformatics and experimental analyses have suggested the interesting possibility that G-quadruplex motifs could be cis-regulatory elements. Here, we identified a characteristic potential G-quadruplex-forming sequence element within the promoter of human thymidine kinase 1 (TK1). Our NMR, UV and CD spectroscopy and gel electrophoresis data suggested that this sequence forms a novel intramolecular G-quadruplex with two G-tetrads in K(+) solution. The results presented here indicate the role of this G-quadruplex motif in transcription of TK1 in cell-based reporter assays. Specific nucleotide substitutions designed to destabilize the G-quadruplex motif resulted in increased promoter activity, supporting direct involvement of the G-quadruplex motif in transcription of TK1. These studies suggest that the G-quadruplex motif may be an important target for controlling critical biological processes, such as DNA synthesis, mediated by TK1.