Human Telomere G-Quadruplexes with Five Repeats Accommodate 8-Oxo-7,8-dihydroguanine by Looping out the DNA Damage.

ABSTRACT: Inflammation and oxidative stress generate free radicals that oxidize guanine (G) in DNA to 8-oxo-7,8-dihydroguanine (OG), and this reaction is prominent in the G-rich telomere sequence. In telomeres, OG is not efficiently removed by repair pathways allowing its concentration to build, surprisingly without any immediate negative consequences to stability. Herein, OG was synthesized in five repeats of the human telomere sequence (TTAGGG)n, at the 5'-G of the 5'-most, middle, and 3'-most G tracks, representing hotspots for oxidation. These synthetic oligomers were folded in relevant amounts of K(+)/Na(+) to adopt hybrid G-quadruplex folds. The structural impact of OG was assayed by circular dichroism, thermal melting, (1)H NMR, and single-molecule profiling by the α-hemolysin nanopore. On th

SUBMITTER: An N 

PROVIDER: S-EPMC4828913 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature