tailieunhanh - Báo cáo khoa học: Human telomeric G-quadruplex: thermodynamic and kinetic studies of telomeric quadruplex stability

The 3¢-ends of human chromosomal DNA terminate in short single-stranded guanine-rich tandem-repeat sequences. In cancer cells, these are associated with the telomere-maintenance enzyme telomerase together with the end-binding protein hPOT1. | MINIREVIEW Human telomeric G-quadruplex thermodynamic and kinetic studies of telomeric quadruplex stability Jonathan B. Chaires James Graham Brown Cancer Center University of Louisville Kentucky KY USA Keywords allostery calorimetry enthalpy entropy folding free energy kinetics quadruplex DNA spectroscopy thermodynamics Correspondence J. B. Chaires James Graham Brown Cancer Center University of Louisville 529 S. Jackson Street Louisville KY 40202 USA Fax 1 502 852 1153 Tel 1 502 852 1172 E-mail Thermodynamic and kinetic studies complement high-resolution structures of G-quadruplexes. Such studies are essential for a thorough understanding of the mechanisms that govern quadruplex folding and conformational changes in quadruplexes. This perspective article reviews representative thermodynamic and kinetic studies of the folding of human telomeric quadruplex structures. Published thermodynamic data vary widely and are inconsistent possible reasons for these inconsistencies are discussed. The key issue of whether such folding reactions are a simple two-state process is examined. A tentative energy balance for the folding of telomeric quad-ruplexes in Na and K solution and for the conformational transition between these forms is presented. Received 25 June 2009 revised 26 August 2009 accepted 17 September 2009 doi Introduction Human telomeric DNA consists of several kilobases of tandem repeats of the sequence 5 -TTAGGG including a terminal single-stranded overhang of 200 nucleotides. This overhang can fold into a variety of quadruplex structures the exact nature of which is under active and intensive investigation. An authoritative review of human telomere molecular biology and pharmacology appeared recently 1 . Telomeric quad-ruplexes are an attractive target for cancer chemotherapy 2-8 . Companion minireviews by Neidle 9 and Arora et al. 10 discuss drug and ligand binding to telomeric quadruplexes in detail. .