Why does DNA need a fifth letter?
Geneticists have discovered an unusual "fifth letter" of DNA in the genome of mice
RIA News The classic set of four "letters"-nucleotides that form the basis of the genetic code, can be expanded to five thanks to the discovery of a special "letter"-a regulator of gene activity in the DNA of mice, geneticists say in an article published in the journal Nature Chemical Biology (Bachman et al., 5-Formylcytosine can be a stable DNA modification in mammals).
"Initially, we thought that these "letters" were one of the short-lived intermediate versions of cytidine. We were able to show that they maintain stability inside living cells, and most likely control the activity of genes and other events in the life of the cell," says Shankar Balasubramanian from the University of Cambridge (in a press release Expanding the DNA alphabet: 'extra' DNA base found to be stable in mammals – VM).
As the scientist explains, this "letter", which geneticists call 5-formylcytosine (5fC), has been known to biologists for a long time, but no one suspected that this molecule could be an independent part of the genetic "alphabet". (The structure of the 5fC molecule from the commentary to the article published in the journal Chemical & Engineering News: Sarah Everts, Modified DNA Base 5-Formylcytosine Has A Specific Biological Role – VM.)
Before the discovery of British geneticists, scientists believed that 5fC molecules were a form of cytosine – one of the four "letters" of DNA. Cytosine temporarily turns into 5-formylcytosine, as geneticists believed, during the application of so–called epigenetic "tags" - a special form of cellular memory that controls the activity of genes in a non-genetic way.
Balasubramanian and his colleagues decided to find out how such labels are applied, in which tissues of the body they are present, and how long they can remain in this form if the process of "rewriting" epigenetic memory is stopped. To do this, geneticists counted all the unusual versions of cytosine in the DNA of different mouse cells and tracked their evolution.
The results of these observations were quite unexpected. It turned out that 5fC molecules are present in all tissues of the body, although in very small quantities – one such "letter" per million ordinary nucleotides, and at the same time retain chemical stability throughout the life of the cell, without changing or renewing.
This fact, according to British geneticists, suggests that 5fC is not an ordinary epigenetic label, but a completely different thing – a special "fifth letter" of DNA that controls the readability and activity of the entire gene as a whole.
"An ordinary DNA strand interacts with a certain set of proteins, and the appearance of 5fC molecules can noticeably change the nature of these reactions, directly or indirectly, changing the shape of the double helix. A different shape and degree of "twisting" of the strand means that DNA will interact with a different set of proteins and auxiliary molecules, which can change how a particular gene works and how active it is," said Martin Bachman, a colleague of Balasubramaniyan.
Geneticists have no doubt that the "fifth letter" of DNA plays other roles in the work of cells, in addition to controlling the activity of genes. They plan to reveal them during the next experiments.
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23.06.2015