title: Role of base excision repair in maintaining the genetic and epigenetic integrity of CpG sites.
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.
authors.affiliation: Cancer Epigenetics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States. Electronic address: Alfonso.Bellacosa@fccc.edu.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bellacosa
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD 21201, United States. Electronic address: adrohat@som.umaryland.edu.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Drohat
mesh_terms: D044503:5-Methylcytosine / Q000737:chemistry / Q000378:metabolism; D018899:CpG Islands; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation; D004260:DNA Repair; D003641:Deamination; D004706:Endodeoxyribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D044502:Thymine DNA Glycosylase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D044503:5-Methylcytosine; D004247:DNA; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human; D044502:Thymine DNA Glycosylase
keywords: 5-Methylcytosine; Base excision repair; CpG site; DNA glycosylase; Deamination; Demethylation; G·T mispair; Methyl binding domain 4; Oxidation; Thymine DNA glycosylase