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A novel G‐quadruplex motif modulates promoter activity of human thymidine kinase 1
Author(s) -
Basundra Richa,
Kumar Akinchan,
Amrane Samir,
Verma Anjali,
Phan Anh Tuân,
Chowdhury Shantanu
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07814.x
Subject(s) - g quadruplex , sequence motif , dna , structural motif , transcription (linguistics) , microbiology and biotechnology , biology , promoter , chemistry , genetics , biochemistry , gene , gene expression , linguistics , philosophy
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 .