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Active DNA demethylation by DNA repair: Facts and uncertainties.

  • Schuermann D Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
  • Weber AR Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
  • Schär P Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland. Electronic address: primo.schaer@unibas.ch.
  • 2016-06-02
Published in:
  • DNA repair. - 2016
AID
Active DNA demethylation
Base excision repair
DNA methylation
DNA repair
Gadd45a
MBD4
NEIL1-3
TDG
TET1
TET2
TET3
UNG2
5-Methylcytosine
Animals
Cellular Reprogramming
DNA
DNA Damage
DNA Glycosylases
DNA Methylation
DNA Repair
Embryo, Mammalian
Epigenesis, Genetic
Humans
Mixed Function Oxygenases
Multigene Family
Pluripotent Stem Cells
Proto-Oncogene Proteins
English Pathways that control and modulate DNA methylation patterning in mammalian cells were poorly understood for a long time, although their importance in establishing and maintaining cell type-specific gene expression was well recognized. The discovery of proteins capable of converting 5-methylcytosine (5mC) to putative substrates for DNA repair introduced a novel and exciting conceptual framework for the investigation and ultimate discovery of molecular mechanisms of DNA demethylation. Against the prevailing notion that DNA methylation is a static epigenetic mark, it turned out to be dynamic and distinct mechanisms appear to have evolved to effect global and locus-specific DNA demethylation. There is compelling evidence that DNA repair, in particular base excision repair, contributes significantly to the turnover of 5mC in cells. By actively demethylating DNA, DNA repair supports the developmental establishment as well as the maintenance of DNA methylation landscapes and gene expression patterns. Yet, while the biochemical pathways are relatively well-established and reviewed, the biological context, function and regulation of DNA repair-mediated active DNA demethylation remains uncertain. In this review, we will thus summarize and critically discuss the evidence that associates active DNA demethylation by DNA repair with specific functional contexts including the DNA methylation erasure in the early embryo, the control of pluripotency and cellular differentiation, the maintenance of cell identity, and the nuclear reprogramming.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/232172
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