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

作者：Basundra Richa; Kumar Akinchan; Amrane Samir; Verma Anjali; Phan Anh Tuan; Chowdhury Shantanu^*

来源：FEBS Journal, 2010, 277(20): 4254-4264.

DOI：10.1111/j.1742-4658.2010.07814.x

• G-quadruplex
• NMR
• thymidine kinase 1

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.

• 出版日期2010-10
• 单位南阳理工学院