TY - CHAP
T1 - Recent Advances on DNA Base Flipping
T2 - A General Mechanism for Writing, Reading, and Erasing DNA Modifications
AU - Ren, Ren
AU - Horton, John R.
AU - Hong, Samuel
AU - Cheng, Xiaodong
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
PY - 2022
Y1 - 2022
N2 - 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, several 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.
AB - 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, several 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.
KW - DNA base flipping
KW - Demethylases
KW - Epigenetic methylation
KW - Methyltransferases
KW - Reader, writer and eraser of DNA methyl marks
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U2 - 10.1007/978-3-031-11454-0_12
DO - 10.1007/978-3-031-11454-0_12
M3 - Chapter
C2 - 36350515
AN - SCOPUS:85141445263
T3 - Advances in Experimental Medicine and Biology
SP - 295
EP - 315
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -