Possible 5th DNA base discovered

th (1)Scientists from Cancer Research UK Cambridge Institute have recently published in Nature Chemical Biologythe discovery of what could be the fifth DNA base, 5-formylcytosine (5fC ). The chemical modification is more stable in mammals than previously thought and could have unforeseen functional roles in the cell.

DNA is made up of four bases: Guanine, Cytosine, Adenine and Thymine. The order in which they are in the DNA strand determines our genetic information. But there is an additional layer of information: chemical modifications on the bases -or on the histones, the proteins that help to pack the DNA- like methylations or acetylations can affect the structure of the DNA and change its accessibility to cellular machinery. This is how genes are turned on and off, and genetically identical cells can become phenotypically different. It has profound implications in development and in an adult´s gene expression. These modifications are influenced by environmental cues, and can be passed on to descendants. This means that lyfestyle can have effects on future generations. The discipline that studies these effects is called epigenetics.

5fC is a rare base found in mammalian DNA and an intermediate in the process of cytosine demethylation. It was thought to be a transient form of cytosine that helped to regulate gene expression. But the in vivo studies lead by Dr. Balasubramanian show that the developmental levels of 5fC differ from those of 5-hydroxymethylcytosine (5hmc), and isotope labelling experiments showed that 5fC can be a stable modification.

The 5fC modification is found in every tissue of the mice, although at very low levels. The position it occupies in the genome, usually in places that regulate gene expression, suggests a specific role as a regulator.

Dr. Balasubramanian affirms that this discovery will change the study of development and the perceived role of these modifications in certain diseases.

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