Spectroscopic insights into quadruplexes of five-repeat telomere DNA sequences upon G-block damage

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 11; pp. 2750 - 2757
• Main Authors: Dvořáková, Zuzana, Vorlíčková, Michaela, Renčiuk, Daniel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2017
• Subjects: Abasic lesion; Circular Dichroism; circular dichroism spectroscopy; DNA; DNA damage; DNA mutation; electrophoresis; extrusion; G-Quadruplexes - drug effects; guanine; Guanine - chemistry; Guanine quadruplex; Human telomere; Humans; melting; Nucleic Acid Conformation - drug effects; nucleotide sequences; Oxidative Stress - genetics; Point Mutation; polyacrylamide; potassium; Repetitive Sequences, Nucleic Acid - genetics; sodium; Sodium - toxicity; Spectroscopy, Near-Infrared; Telomere - chemistry; Telomere - drug effects; Telomere - genetics; telomeres; ultraviolet-visible spectroscopy; Human telomere; DNA mutation; Abasic lesion; Guanine quadruplex; Circular dichroism
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.07.019

The DNA lesions, resulting from oxidative damage, were shown to destabilize human telomere four-repeat quadruplex and to alter its structure. Long telomere DNA, as a repetitive sequence, offers, however, other mechanisms of dealing with the lesion: extrusion of the damaged repeat into loop or shifting the quadruplex position by one repeat. Using circular dichroism and UV absorption spectroscopy and polyacrylamide electrophoresis, we studied consequences of lesions at different positions of the model five-repeat human telomere DNA sequences on the structure and stability of their quadruplexes in sodium and in potassium. The repeats affected by lesion are preferentially positioned as terminal overhangs of the core quadruplex structurally similar to the four-repeat one. Forced affecting of the inner repeats leads to presence of variety of more parallel folds in potassium. In sodium the designed models form mixture of two dominant antiparallel quadruplexes whose population varies with the position of the affected repeat. The shapes of quadruplex CD spectra, namely the height of dominant peaks, significantly correlate with melting temperatures. Lesion in one guanine tract of a more than four repeats long human telomere DNA sequence may cause re-positioning of its quadruplex arrangement associated with a shift of the structure to less common quadruplex conformations. The type of the quadruplex depends on the loop position and external conditions. The telomere DNA quadruplexes are quite resistant to the effect of point mutations due to the telomere DNA repetitive nature, although their structure and, consequently, function might be altered. •We studied the effect of G-lesions on quadruplex of five-repeat human telomere DNA.•The mutated repeat is preferably positioned out of the quadruplex core as overhang.•Mutated inner repeats are extruded into loops leading to more parallel folds in K+.•Variable population of antiparallel quadruplexes is formed in Na+.•The height of the dominant CD peak correlates with quadruplex thermal stability.