title: A novel G-quadruplex motif modulates promoter activity of human thymidine kinase 1.
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.
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Basundra
authors.forename: Akinchan
authors.initials: A
authors.lastname: Kumar
authors.forename: Samir
authors.initials: S
authors.lastname: Amrane
authors.forename: Anjali
authors.initials: A
authors.lastname: Verma
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
authors.forename: Shantanu
authors.initials: S
authors.lastname: Chowdhury
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D009690:Nucleic Acid Conformation; D011188:Potassium; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012996:Solutions; D013057:Spectrum Analysis; D013937:Thymidine Kinase / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012996:Solutions; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D011188:Potassium