Formation and biological consequences of 5-Formylcytosine in genomic DNA

5-Formyl-2′-deoxycytidine (5fdC) is a naturally occurring nucleobase that is broadly distributed in genomic DNA. 5fdC is produced via the oxidation of 5-methylcytosine (5mdC) by ten-eleven translocation enzyme (TET) and can be further converted to 5-carboxylcytosine (5cadC) by TET. Both 5fdC and 5cadC can be restored to dC by TDG-mediated base excision repair and direct deformylation/decarboxylation. Thus, 5fdC is considered an intermediate in the TET-mediated DNA demethylation pathway. 5fdC also alters the structure and stability of genomic DNA and affects genetic expression. This review summarizes the recent research on 5fdC, detailing its formation, detection and distribution, biological functions and transformation in cells. The challenges and future prospects to further explore the function and metabolism of 5fdC are briefly discussed at the end.