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Figure: A simulated model for one possible structure for iCD-DNA—a braided triplex.

A new kind of DNA structure from a disease-linked gene

The discovery For many, the irresistible attraction of research is the potential for discovery that each day brings. Researchers in the lab of Dipankar Sen at Simon Fraser University recently unearthed one of those unexpected, astonishing results. In the course of studying how a repetitive nucleic acid sequence from a disease-causing gene forms secondary structures known as G-quadruplexes, Ph.D. student Prince Kumar Lat examined the DNA sequence using circular dichroism (CD) spectroscopy. To his surprise, the results showed that a dramatic inversion of the DNA structure had taken place.  A discovery in the early 1980’s of a similar structural inversion introduced the world to a double helical structure called “Z-DNA”, which is a left-handed double-helix induced by an alternating sequence of cytosine (C) and guanine (G) bases (i.e. ...CGCGCGCG...). The Sen lab’s newly discovered DNA structure (called "iCD-DNA") has a characteristic CD spectrum that is also inverted but wholly different from that of Z-DNA. And its repeating sequence ...CCGGGGCCGGGGCCGGGG... does not follow the strict rules that have been established for the formation of Z-DNA.

Its significance – An intriguing outcome of this discovery is the potential for a direct link between the possible formation of iCD-DNA in the cell and the disease state;  if so, this connection could lead to new strategies for developing therapeutics.  Aside from the healthcare-related implications of this study, the discovery of new forms of DNA opens up new areas of research.  One of the latter, almost certainly, will be in the burgeoning field of DNA nanotechnology.

Read the paper“(C2G4)n repeat expansion sequences from the C9orf72gene form an unusual DNA higher-order structure in the pH range of 5-6 ” by P. K. Lat and D. Sen. PLOS One 13(6): e0198418 (2018) DOI:  https://doi.org/10.1371/journal.pone.0198418

Website article compiled by Jacqueline Watson with Theresa Kitos