5-Formylcytosine (5fC) is a

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

nitrogen base derived from

cytosine Cytosine () (symbol C or Cyt) is one of the four nucleotide bases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attac ...

. In the context of nucleic acid chemistry and biology, it is regarded as an epigenetic marker. Discovered in 2011 in mammalian embryonic stem cells by Thomas Carell's research group the modified nucleoside was more recently confirmed to be relevant both as an intermediate in the active demethylation pathway and as a standalone epigenetic marker. In mammals, 5fC is formed by oxidation of

5-hydroxymethylcytosine 5-Hydroxymethylcytosine (5hmC) is a DNA pyrimidine nitrogen base derived from cytosine. It is potentially important in epigenetics, because the hydroxymethyl group on the cytosine can possibly switch a gene on and off. It was first seen in bact ...

(5hmC) a reaction mediated by

TET enzymes The TET enzymes are a family of ten-eleven translocation (TET) 5-Methylcytosine, methylcytosine dioxygenases. They are instrumental in DNA demethylation. 5-Methylcytosine (see first Figure) is a methylation, methylated form of the DNA base cytosin ...

. Its molecular formula is C₅H₅N₃O_2.

Localization

Similarly to the related cytosine modifications

5-methylcytosine 5-Methylcytosine (5mC) is a methylation, methylated form of the DNA base cytosine (C) that regulates gene Transcription (genetics), transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same s ...

(5mC) and 5hmC, 5fC is broadly distributed across the mammalian genome, although it is much more rarely occurring. The specific concentration values vary significantly depending on the cell type. 5fC can be aberrantly expressed in distinct sets of tissue that can indicate different tumor onsets and canceration.

Functions

The exact functions of 5fC have not been yet precisely defined, although it is likely to play key roles in at least two distinct frameworks. Firstly, 5fC serves as an intermediate of the active

demethylation Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen at ...

pathway, a process that contributes to the DNA maintenance and integrity by replacing 5mC with canonical cytosine. A central dilemma regarding 5fC (and epigenetics in general) is how reader proteins recognise their substrates with such high specificity over the overwhelming background. Thymine-DNA glycosylase (TDG), a protein which is involved in the removal of 5fC from DNA in mammals, is especially interesting in this context. Secondly, 5fC can exist as an independent, stable modification, but its role in this context is still blurry.

5fC impact on DNA structure and flexibility

The understanding of the impact of 5fC on DNA physical properties is to date limited. Recent studies have reported contradictory findings regarding the structural impact of 5fC on DNA. On the other hand, several researchers working independently have identified 5fC to distinctly increase DNA flexibility. 5fC also curtails DNA double helix stability and increases base pair opening.

References

{{DEFAULTSORT:Hydroxymethylcytosine, 5- Pyrimidones Nucleobases

Localization

Functions

5fC impact on DNA structure and flexibility

See also

References