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Role of base excision repair in maintaining the genetic and epigenetic integrity of CpG sites
Affiliation:1. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA;2. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
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:Base excision repair  DNA glycosylase  Deamination  Oxidation  Demethylation  5-Methylcytosine  CpG site  Methyl binding domain 4  Thymine DNA glycosylase  G·T mispair
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