DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications.
The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified bases from prokaryotes and eukaryotes. Despite significant differences in structures and functions, they are remarkably similar regarding their engagement in flipping a target base/nucleotide within DNA for specific recognitions and/or reactions. We thus highlight base flipping as a common structural framework broadly applied by distinct classes of proteins and enzymes across phyla for epigenetic regulations of DNA.
Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA. shong27@emory.edu.|Molecular and Systems Pharmacology Graduate Program, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA. shong27@emory.edu.
Samuel
S
Hong
Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA.
Xiaodong
X
Cheng
D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D000225:Adenine / Q000737:chemistry / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D044127:Epigenesis, Genetic; D056890:Eukaryota / Q000378:metabolism; D011387:Prokaryotic Cells / Q000378:metabolism; D000072417:Protein Domains / Q000235:genetics
C560974:5-carboxylcytosine; C560973:5-formylcytosine; D004268:DNA-Binding Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA; D000225:Adenine