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DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications

  • Samuel Hong
  • Xiaodong Cheng
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 945)

Abstract

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.

Keywords

Epigenetic Signal Base Excision Repair Pathway Active Site Pocket Target Base Target Recognition Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

5caC

5-Carboxylcytosine

5fC

5-Formylcytosine

5ghmC

Glucosylated 5-hydroxymethylcytosine

5hmC

5-Hydroxymethylcytosine

5mC

5-Methylcytosine

AdoHcy

S-Adenosyl-l-homocysteine

AdoMet

S-Adenosyl-l-methionine

AlkB

E. coli alkylated DNA repair protein

ALKBH5

Alkylated DNA repair protein AlkB homolog 5 in human

CMT2

Chromomethylase 2 (plant specific)

CMT3

Chromomethylase 3 (plant specific)

DME

Demeter (plant)

DML3

Demeter-like protein 3 (plant)

DNMT1

Mammalian DNA methyltransferase 1

DNMT3A

Mammalian DNA methyltransferase 3A

DNMT3L

Mammalian DNA methyltransferase 3-like

DRM2

Domain rearranged methyltransferase 2 (plant)

FTO

Fat mass and obesity-associated protein

HhH

Helix-hairpin-helix

JBP

J-binding protein

MBD

Methyl-CpG-binding domain

McrB

Modified cytosine restriction B

Met1

DNA methyltransferase 1 (plant)

MTase

Methyltransferase

N4mC

N4-methylcytosine

N6mA

N6-methyladenine

NOG

N-oxalylglycine

ROS1

Repressor of silencing 1 (plant specific)

SRA

SET and RING associated

TDG

Thymine DNA glycosylase

TET

Ten-eleven translocation

TRD

Target recognition domain

Uhrf1

Ubiquitin-like-containing PHD and RING finger domains protein 1

WH

Winged helix

αKG

α-Ketoglutarate

Notes

Acknowledgments

The work in the authors’ laboratory is supported by grant from National Institutes of Health (GM049245-22). X.C. is a Georgia Research Alliance Eminent Scholar.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of BiochemistryEmory University School of MedicineAtlantaUSA
  2. 2.Molecular and Systems Pharmacology Graduate ProgramEmory University School of MedicineAtlantaUSA

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