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Royal Society of Chemistry, Organic and Biomolecular Chemistry, 27(13), p. 7421-7429

DOI: 10.1039/c5ob00748h

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The oxidative damage to the human telomere: effects of 5-hydroxymethyl-2′-deoxyuridine on telomeric G-quadruplex structures

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Abstract

As part of the genome, human telomeric regions can be damaged by chemically reactive molecules responsible for oxidative DNA damages. Considering that G-quadruplex structures have been proven to occur in human telomere regions, several researches have been devoted to investigate the effect of oxidation products on the properties of these structures. However only investigations concerning the presence in G-quadruplexes of the main oxidation products of deoxyguanosine and deoxyadenosine have appeared in literature. Here, we investigated the effects of 5-hydroxymethyl-2'-deoxyuridine (5-hmdU), one of the main oxidation product of T, on the physical-chemical properties of the G-quadruplex structures formed by two human telomeric sequences. Collected calorimetric, circular dichroism and electrophoretic data suggest that, contrarily to most of the results about other damages, the replacement of a T with a 5-hmdU results only in negligible effects on the structural stability. Reported results and other data from literature suggest a possible protecting effect of the loop residues on the other parts of the G-quadruplexes.