Wednesday, December 3, 2014

Four-stranded DNA

Time for some different DNA science - lets leave 'barcoding' out for a post and focus on DNA structure. While browsing through recent science news and publication announcements I stumbled over a paper on G-quadruplex motifs in the Maize genome. I admit I had to look this term up myself as I probably heard about it only once a while back and never followed any new research in that field despite the fact that it is really fascinating. 

The year 1953 marks the big breakthrough in our understanding of DNA as two connected strands known as the double helix. It is the year in which the famous Watson & Crick paper appeared in Nature. As a result just these two names are usually mentioned although there should be four (and they appear in papers within the same issue). There was also Maurice Wilkins who together with Watson and Crick received the Nobel Prize in physiology or medicine for the determination of the structure of DNA, but proper credit was never given to a very important contributor, Rosalind Franklin, respected authority in X-ray crystallography (which made the entire theory possible) and the only of the four researchers that had any degrees in chemistry. She was not properly credited for here contribution for a long time. Unfortunately, this is not the only example of women in science being marginalized, despite the importance of their work.

But back to the DNA structure. We know that the strands that make the double helix regularly separate so they e.g. can replicate. We also know for a while that the DNA comes in different conformations (e.g. A-DNA, B-DNA, and Z-DNA forms). Since the 1990s researchers have been looking at alternative shapes DNA can also twist into. One of those is the G-quadruplex, which is DNA rich in guanine and capable of forming a four-stranded structure. Four guanine bases can associate through hydrogen bonding to form a square planar structure, and two or more of those tetrads can stack on top of each other to form a G-quadruplex (G4 motif, see image). The quadruplex structure is further stabilized by the presence of a cation, especially potassium, which sits in a central channel between each pair of tetrads.

G-quadruplexes have been described as structures in search of a function, as for many years there was minimal evidence pointing towards a biological role for these structures. However, more recently they 

G-quadruplexes are present in genes that regulate cancer and cell division in humans, making it an important focus in scientific research. But not much is known about them. Only more recently they have been connected to immunoglobulin heavy chain switching and telomerase activity. The latter has implications for cancer regulation and made G-quadruplexes an important focus in scientific research. 

The authors of the aforementioned new paper wanted to know if certain the four-strand G-quadruplex DNA might exist throughout the genome of maize. They found 150,000 sequence motifs that could theoretically adopt the G-quadruplex structure, and those were distributed all over the chromosomes. Further examination showed that they were present in very specific places, as opposed to a random distribution. Given this strategic placement, the structure is likely to perform some sort of function:

Taken together, these data support a new hypothesis for functional significance of G4 motifs in maize and potentially elsewhere. Analysis of G4 motif distribution revealed their widespread association with genes for adjustment of cellular energy status, especially under extreme conditions. On the basis of these observations, we propose that G4 motifs reflect a previously unrecognized but widely conserved set of DNA sequences that could function in regulating genes central to the energy state of the cell.

The researchers believe that G-quadruplexes are part of a machinery that allows an organism to turn hundreds of genes off or on for example in response to stress. Very exciting new research and yet another good example for the fact that we don't know nearly as much about genomes as we would like to.

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