DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation

Dengke K. Ma, Junjie U. Guo, Guo Li Ming, Hongjun Song

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1526-1531
Number of pages6
JournalCell cycle (Georgetown, Tex.)
Volume8
Issue number10
StatePublished - May 15 2009

Keywords

  • 5-methylcytosine
  • Base excision repair
  • Deaminase
  • DNA demethylation
  • Gadd45
  • Gadd45a
  • Gadd45b
  • Gadd45g
  • Glycosylase
  • Nucleotide excision repair

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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