Abstract

DNA sequences called telomeres, located at the ends of chromosomes, fold into compact structures called G-quadruplexes. These structures are named for the four repeated sequences of the nucleotide guanine that characterize telomeric DNA and shape the folding of the quadruplex. Cynthia J. Burrows, a chemist at the University of Utah and a recently elected member of the National Academy of Sciences, studies chemical modifications to damage-prone DNA structures, such as G-quadruplexes, and the mechanisms of folding and unfolding in these important DNA regions. By attaching DNA tails to G-quadruplexes and threading the tails through a hollow, mushroom-shaped α-hemolysin nanopore, Burrows and her colleagues examined how different folding structures affected quadruplex unraveling in a confined space. Burrows recently spoke to PNAS about her findings. Cynthia J. Burrows. Image courtesy of Alyssa Geisler. > PNAS: What does the work described in your Inaugural Article (1) reveal about G-quadruplexes? > Burrows: We’re working with the human telomere sequence GGGTTA, repeated at least four times. You need 12 guanines all together to fold up into this G-quadruplex. If we put this sequence into physiological salt conditions, mostly potassium, the sequence will fold into a hybrid fold. If you only have sodium present as the cation, then things wrap around a little bit differently and you end up with a basket fold. If you …

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