TY - JOUR
T1 - MBD4 and TDG
T2 - Multifaceted DNA glycosylases with ever expanding biological roles
AU - Sjolund, Ashley B.
AU - Senejani, Alireza G.
AU - Sweasy, Joann B.
N1 - Funding Information:
We apologize in advance if relevant articles were missed or not included in this extensive review. This research was supported by the National Institutes of Health ( P01 CA129186 ).
PY - 2013/3
Y1 - 2013/3
N2 - The base excision repair system is vital to the repair of endogenous and exogenous DNA damage. This pathway is initiated by one of several DNA glycosylases that recognizes and excises specific DNA lesions in a coordinated fashion. Methyl-CpG Domain Protein 4 (MBD4) and Thymine DNA Glycosylase (TDG) are the two major G:T glycosylases that remove thymine generated by the deamination of 5-methylcytosine. Both of these glycosylases also remove a variety of other base lesions, including G:U and preferentially act at CpG sites throughout the genome. Many have questioned the purpose of seemingly redundant glycosylases, but new information has emerged to suggest MBD4 and TDG have diverse biological functions. MBD4 has been closely linked to apoptosis, while TDG has been clearly implicated in transcriptional regulation. This article reviews all of these developments, and discusses the consequences of germline and somatic mutations that lead to non-synonymous amino acid substitutions on MBD4 and TDG protein function. In addition, we report the finding of alternatively spliced variants of MBD4 and TDG and the results of functional studies of a tumor-associated variant of MBD4.
AB - The base excision repair system is vital to the repair of endogenous and exogenous DNA damage. This pathway is initiated by one of several DNA glycosylases that recognizes and excises specific DNA lesions in a coordinated fashion. Methyl-CpG Domain Protein 4 (MBD4) and Thymine DNA Glycosylase (TDG) are the two major G:T glycosylases that remove thymine generated by the deamination of 5-methylcytosine. Both of these glycosylases also remove a variety of other base lesions, including G:U and preferentially act at CpG sites throughout the genome. Many have questioned the purpose of seemingly redundant glycosylases, but new information has emerged to suggest MBD4 and TDG have diverse biological functions. MBD4 has been closely linked to apoptosis, while TDG has been clearly implicated in transcriptional regulation. This article reviews all of these developments, and discusses the consequences of germline and somatic mutations that lead to non-synonymous amino acid substitutions on MBD4 and TDG protein function. In addition, we report the finding of alternatively spliced variants of MBD4 and TDG and the results of functional studies of a tumor-associated variant of MBD4.
KW - Base excision repair
KW - DNA glycosylase
KW - DNA methylation
KW - Polymorphisms
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U2 - 10.1016/j.mrfmmm.2012.11.001
DO - 10.1016/j.mrfmmm.2012.11.001
M3 - Review article
C2 - 23195996
AN - SCOPUS:84877927182
SN - 0027-5107
VL - 743-744
SP - 12
EP - 25
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
ER -