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Updated: Aug 13, 2026

Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter
Anh Tuân Phan1, Vitaly Kuryavyi, Hai Yan Gaw
1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. phantuan@mskcc.org
Abstract:
It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres.
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