Role of base excision repair in maintaining the genetic and epigenetic integrity of CpG sites

DNA Repair (Amst). 2015 Aug:32:33-42. doi: 10.1016/j.dnarep.2015.04.011. Epub 2015 May 1.

Abstract

Cytosine methylation at CpG dinucleotides is a central component of epigenetic regulation in vertebrates, and the base excision repair (BER) pathway is important for maintaining both the genetic stability and the methylation status of CpG sites. This perspective focuses on two enzymes that are of particular importance for the genetic and epigenetic integrity of CpG sites, methyl binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). We discuss their capacity for countering C to T mutations at CpG sites, by initiating base excision repair of G · T mismatches generated by deamination of 5-methylcytosine (5mC). We also consider their role in active DNA demethylation, including pathways that are initiated by oxidation and/or deamination of 5mC.

Keywords: 5-Methylcytosine; Base excision repair; CpG site; DNA glycosylase; Deamination; Demethylation; G·T mispair; Methyl binding domain 4; Oxidation; Thymine DNA glycosylase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • 5-Methylcytosine / chemistry
  • 5-Methylcytosine / metabolism
  • CpG Islands*
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Methylation
  • DNA Repair*
  • Deamination
  • Endodeoxyribonucleases / chemistry*
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism
  • Epigenesis, Genetic*
  • Humans
  • Models, Molecular
  • Oxidation-Reduction
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thymine DNA Glycosylase / chemistry*
  • Thymine DNA Glycosylase / genetics
  • Thymine DNA Glycosylase / metabolism

Substances

  • 5-Methylcytosine
  • DNA
  • Endodeoxyribonucleases
  • MBD4 protein, human
  • Thymine DNA Glycosylase