Induction of parallel human telomeric G-quadruplex structures by Sr(2+).
Human telomeric DNA forms G-quadruplex secondary structures, which can inhibit telomerase activity and are targets for anti-cancer drugs. Here we show that Sr(2+) can induce human telomeric DNA to form both inter- and intramolecular structures having characteristics consistent with G-quadruplexes. Unlike Na(+) or K(+), Sr(2+) facilitated intermolecular structure formation for oligonucleotides with 2 to 5 5'-d(TTAGGG)-3' repeats. Longer 5'-d(TTAGGG)-3' oligonucleotides formed exclusively intramolecular structures. Altering the 5'-d(TTAGGG)-3' to 5'-d(TTAGAG)-3' in the 1st, 3rd, or 4th repeats of 5'-d(TTAGGG)(4)-3' stabilized the formation of intermolecular structures. However, a more compact, intramolecular structure was still observed when the 2nd repeat was altered. Circular dichroism spectroscopy results suggest that the structures were parallel-stranded, distinguishing them from similar DNA sequences in Na(+) and K(+). This study shows that Sr(2+), promotes parallel-stranded, inter- and intramolecular G-quadruplexes that can serve as models to study DNA substrate recognition by telomerase.
Pedroso
Ilene M
IM
Department of Biochemistry and Molecular Biology, University of Miami, School of Medicine, P.O. Box 016129 (R629), Miami, FL 33101-6129, USA.
Duarte
Luis F
LF
Yanez
Giscard
G
Baker
Asmaa M
AM
Fletcher
Terace M
TM
D002413:Cations, Divalent; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D006147:Guanine / Q000737:chemistry; D006801:Humans; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D013324:Strontium / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry*
D002413:Cations, Divalent; D009841:Oligonucleotides; D006147:Guanine; D004247:DNA; D012964:Sodium; D011188:Potassium; D013324:Strontium