New shape of DNA found in human cells

By Dr. Ananya Mandal, MDApr 25 2018

DNA double helix discovery is one of the major breakthroughs in human scientific history. Now in a new research, scientists have found that there may be another new shape in the DNA machinery within the cells of humans. The findings of this research titled, “I-motif DNA structures are formed in the nuclei of human cells,” appeared this week in the latest issue of the journal Nature Chemistry. Their scope in human health and disease remains to be explored.

The team of researchers from the Kinghorn Centre for Clinical Genomics at the Garvan Institute of Medical Research in Sydney called this new shape i-motif. The DNA loop typically appeared as a four-stranded knot. They are still trying to understand the role of this new structure within humans.

In earlier studies DNA has been described as triple helices and cruciform in shape but this is the first time that this special i-motif structure has been noted. This structure was reported nearly two decades back in labs where conditions were acidic. It was considered a one off finding which would never be repeated again in nature. Daniel Christ, director for the Centre for Targeted Therapy at the Garvan Institute and a co-author of the new study said that there is now a debate on the relevance of this new structure.

The authors explain that a small section of the DNA double helix comes apart first at the hydrogen bonds that connect them. The helix now untwists from its original shape. If the strand is rich in cytosine instead of any of the other four bases – adenine, thymine or guanine, it proceeds to loop outwards. Now it resembles a tied shoe lace. Normally the cytosine binds to guanine, but in this loop the hydrogen bonds develop between cytosine bases.

For this study the team of researchers prepared an antibody molecule that could bind to the i-motif structure. Then they used fluorescent light to see these tagged structures under microscopes. The team suggests that it could be important for transcription process. Lead researcher Dr Mahdi Zeraati said that when they applied the fluorescent lights, the tagged antibodies lit up. What was exciting was that the green spots that indicated the i-motifs lit up and disappeared one time. This meant that they were “forming, dissolving and forming again,” he said.

Further the motifs also appeared in the promoter regions of the genes. These promoter regions help in turning switches on and off for protein formation. The expressions of these promoter regions could be associated with these new i-motifs say the experts on the team.

The researchers speculate on the impact of this finding on human health and disease and future of drug development that could target these structures in disease. As of now they want to understand the impact of these structures and their role in human physiology. More research and information on the original findings of Watson and Crick are on the way say researchers.