Journal
CELL CYCLE
Volume 8, Issue 10, Pages 1526-1531Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.10.8500
Keywords
DNA demethylation; Gadd45; Gadd45a; Gadd45b; Gadd45g; 5-methylcytosine; deaminase; glycosylase; base excision repair; nucleotide excision repair
Categories
Funding
- National Institute of Health [AG024984, NS047344, MH084018, NS048271]
- March of Dimes
- NARSAD
- MSCRF
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DNA cytosine methylation represents an intrinsic modification signal of the genome that plays important roles in heritable gene silencing, heterochromatin formation and certain trans-generational epigenetic inheritance. In contrast to the process of DNA methylation that is catalyzed by specific classes of methyltransferases, molecular players underlying active DNA demethylation have long been elusive. Emerging biochemical and functional evidence suggests that active DNA demethylation in vertebrates can be mediated through DNA excision repair enzymes, similar to the well-known repair-based DNA demethylation mechanism in Arabidopsis. As key regulators, non-enzymatic Gadd45 proteins function to recruit enzymatic machineries and promote coupling of deamination, base and nucleotide-excision repair in the process of DNA demethylation. In this article, we review recent findings and discuss functional and evolutionary implications of such mechanisms underlying active DNA demethylation.
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