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

Alfonso Bellacosa; Alexander C. Drohat

doi:10.1016/j.dnarep.2015.04.011

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

Alfonso Bellacosa, Alexander C. Drohat

University of Maryland

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

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.

Original language	English
Pages (from-to)	33-42
Number of pages	10
Journal	DNA Repair
Volume	32
DOIs	https://doi.org/10.1016/j.dnarep.2015.04.011
State	Published - Aug 1 2015

Keywords

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

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10.1016/j.dnarep.2015.04.011

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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.",

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AU - Bellacosa, Alfonso

AU - Drohat, Alexander C.

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N2 - 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.

AB - 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.

KW - 5-Methylcytosine/chemistry

KW - CpG Islands

KW - DNA Methylation

KW - DNA Repair

KW - DNA/chemistry

KW - Deamination

KW - Endodeoxyribonucleases/chemistry

KW - Epigenesis, Genetic

KW - Humans

KW - Models, Molecular

KW - Oxidation-Reduction

KW - Protein Structure, Secondary

KW - Protein Structure, Tertiary

KW - Thymine DNA Glycosylase/chemistry

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DO - 10.1016/j.dnarep.2015.04.011

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SN - 1568-7864

VL - 32

SP - 33

EP - 42

JO - DNA Repair

JF - DNA Repair

ER -

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

Abstract

Keywords

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