Jean-Paul Rodriguez
Four DNA strands come together in this model, built using data from x-ray crystallography.
There is no more iconic image in biology than that of DNA's double-stranded helix, which coils and supercoils on itself to form dense chromosomes.
But a quite different, square-shaped type of DNA structure can easily be created in the laboratory by the folding of synthetic DNA strands rich in guanine, one of the building blocks of DNA. A G-quadruplex comprises four guanines from different places along a G-rich strand held together by a special type of hydrogen bonding to form a compact square structure that interrupts the DNA helix.
Scientists have long believed that these so-called 'G-quadruplex structures' may occasionally form in the DNA of living cells, and the first evidence of that surfaced in single-cell organisms in 20091.
In a paper published online today in Nature Chemistry2, researchers led by Shankar Balasubramanian at the University of Cambridge, UK, provide strong evidence that G-quadruplexes do occur in human cells — and that these unusual structures may have important biological functions.
Protecting the chromosome
The protective tips of chromosomal DNA, known as telomeres, are rich in guanine and so are likely candidates for G-quadruplex structures. In fact, studies in cancer cells have shown that small molecules that bind and stabilize G-quadruplex structures cause DNA damage at telomeres, supporting the argument3.
After trawling through human genome data in search of other guanine-rich sequences, some scientists have suggested that quadruplexes could also be created in other areas of the genome involved in regulating genes, particularly some cancer-causing genes.
G-quadruplex visualized
This seems likely to be the case, Balasubramanian and colleagues found. They engineered an antibody that binds tightly and specifically to G-quadruplex structures and does not bind to double-stranded helical DNA. When they incubated the antibody with human cells in culture, they found that it bound to many different sites in the chromosomes, only around a quarter of them in telomeres.
“It’s early days, but if we can map exactly where these G-quadruplex structures pop up in the genome, we may learn how better to control genes or other cellular processes that go awry in diseases like cancer,” he says. “That’s the long-term vision anyway.’’
- Journal name:
- Nature
- DOI:
- doi:10.1038/nature.2013.12253
I do have to ask this question, is it associated with disease, or is it a normal part of DNA replication? It could be that during replication, when the DNA ladder is "unzipped" and being copied, that these naked single strands high in guanine content tend to mingle and form these complexes. Since almost no molecular interaction goes to waste in a cell this must do something. Perhaps this mechanism may be involved in swapping genes from one chromosome to another? Mijas
Cool, but now we need to understand what this does, how its formation is regulated during the cell cycle, is it associated with disease, or is it a normal part of DNA replication? It could be that during replication, when the DNA ladder is "unzipped" and being copied, that these naked single strands high in guanine content tend to mingle and form these complexes. Since almost no molecular interaction goes to waste in a cell this must do something. Perhaps this mechanism may be involved in swapping genes from one chromosome to another? Obviously this would have to be a regulated phenomenon, otherwise our chromosomes would be scrambled by the time we reach adulthood. Perhaps it is a means of defending replicating DNA from transpositions and viral genes that may spread during replication?
It would be very interesting to see where else this structure may be found, in activated immune cells, or brain microglia for instance. New discoveries like this can be very exciting and may lead to answers for previously confusing questions. Science is cool.
It is nice how you want to do it and protect the chromosome in the same time. I am really impressed! For sure this will help many species! At least I will try the Blinds Essex service for my personal needs.
I also was thinking the same way about the square-shaped type of DNA structure can easily be created in the laboratory by the folding of synthetic DNA strands rich in guanine. Directory in UK
I know what you mean and maybe with marketing help for small businesses we can promote it! For sure this will help to cure many more diseases. At least that is my personal opinion!
I don't think that there is no real observance of G-quadruplex as such in paper but evidence from antibody reaction. Even when we consider that antibody does work for large structures like quadruplex, then in such a vast complex of strands in tangled chromosome the probability of four strands coming together. http://www.weblist24.com
It is a well-known fact that, according to recent surveys, public speaking is the number one fear in a person’s life. The fear of public speaking is rated even higher than death, showing just how much one can dread giving a speech. speeches
Nollegio barche made a report for us and it is exactly like you said! In this way we will see an update really soon. And I am sure that we will find new elements in the cells. At least that is my personal opinion.
I read about this aspect, but where can we read more? The Dna structure seems to be somehow different. For example the computational fluid dynamics is different for every specie. And we should be aware of this thing!
I do agree with you Christopher regarding the test tube under certain conditions and then the quadruplexe. easyTether
I think this is an interesting discovery because it's the first time they've been seen in actual cells vs just in vitro. Up until now they've just taken a piece of G-rich DNA, put it in a test tube under certain conditions and then the quadruplexes were seen, but no one knew for sure i f these structures formed in a living system.
Interesting finding if it holds up. Question is, how well does the antibody co-localize with replication- and repair-associated helicases and genomic sites preferentially targeted by pyridostatin.
Interesting finding if it holds up. Question is, how well does the antibody co-localize with replication- and repair-associated helicases and genomic sites preferentially targeted by pyridostatin.
Antibodies to Nucleic acids do not work exactly the same way as does antibodies raised against protein. For example polyclonal antibody raised against N-6 methyladenine is able to recognize SAM which substrate of methyltransferase and give false positive results on Nylon membrane for N-6 methylation reaction. There is no real observance of G-quadruplex as such in paper but evidence from antibody reaction. Even when we consider that antibody does work for large structures like quadruplex, then in such a vast complex of strands in tangled chromosome the probability of four strands coming together (forming simile to a quadruplex) is also high and therefore the results published may be an artifact awaiting scrutiny!