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Formation and biological consequences of 5-Formylcytosine in genomic DNA
Affiliation:1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA;2. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, 77030, USA;3. Robert and Janice McNair Foundation/ McNair Medical Institute M.D./Ph.D. Scholars Program, Baylor College of Medicine, Houston, TX, 77030, USA;4. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA;5. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA;1. Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York, 11794, USA;2. Biochemistry and Structural Biology graduate program, Stony Brook University, New York 11794, USA;3. Stony Brook Cancer Center, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, 11794, USA
Abstract: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.
Keywords:DNA methylation  DNA demethylation  5-Formylcytosine  Detection  Biological function
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