DNA Demethylation by TDG

Abstract

DNA methylation has long been considered a very stable DNA modification in mammals that could only be removed by replication in the absence of remethylation – that is, by mere dilution of this epigenetic mark (so-called passive DNA demethylation). However, in recent years, a significant number of studies have revealed the existence of active processes of DNA demethylation in mammals, with important roles in development and transcriptional regulation, allowing the molecular mechanisms of active DNA demethylation to be unraveled. In this article, we review the recent literature highlighting the prominent role played in active DNA demethylation by base excision repair and especially by TDG.

KEYWORDS::

• 5-carboxylcytosine
• 5-formylcytosine
• 5-hydroxymethylcytosine
• 5-hydroxymethyluracil
• base excision repair
• DNA demethylation
• DNA methylation
• embryonic lethality
• histone modification
• thymine DNA glycosylase

Acknowledgements

The authors would like to thank past and present members of the Bellacosa laboratory for thoughtful comments and open discussions over the years; R Katz and F Roegiers for critical reading of the manuscript; L Larue and his research group for a long-lasting collaboration; and R Sonlin for secretarial assistance.

Financial&competing interests disclosure

National Institutes of Health. This study was supported by NIH grants CA78412 and CA06927, funds from the Pennsylvania Department of Health, and an appropriation from the Commonwealth of Pennsylvania to the Fox Chase Cancer Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

National Institutes of Health. This study was supported by NIH grants CA78412 and CA06927, funds from the Pennsylvania Department of Health, and an appropriation from the Commonwealth of Pennsylvania to the Fox Chase Cancer Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.