title: The enigmatic thymine DNA glycosylase.
abstract: When it was first isolated from extracts of HeLa cells in Josef Jiricny's laboratory, the thymine DNA glycosylase (TDG) attracted attention because of its ability to remove thymine, i.e. a normal DNA base, from G.T mispairs. This implicated a function of DNA base excision repair in the restoration of G.C base pairs following the deamination of a 5-methylcytosine. TDG turned out to be the founding member of a newly emerging family of mismatch-directed uracil-DNA glycosylases, the MUG proteins, that act on a comparably broad spectrum of base lesion including G.U as the common, most efficiently processed substrate. However, because of its apparent catalytic inefficiency, some have considered TDG a poor DNA repair enzyme without an important biological function. Others have reported 5-meC DNA glycosylase activity to be associated with TDG, thrusting the enzyme into limelight as a possible DNA demethylase. Yet others have found the glycosylase to interact with transcription factors, implicating a function in gene regulation, which appears to be critically important in developmental processes. This article reviews all these developments in view of possible biological functions of this multifaceted DNA glycosylase.
authors.affiliation: Centre for Biomedicine, Department of Clinical Biological Research, University of Basel, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cortázar
authors.forename: Christophe
authors.initials: C
authors.lastname: Kunz
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Saito
authors.forename: Roland
authors.initials: R
authors.lastname: Steinacher
authors.forename: Primo
authors.initials: P
authors.lastname: Schär
mesh_terms: D000595:Amino Acid Sequence; D053843:DNA Mismatch Repair; D004260:DNA Repair; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D044502:Thymine DNA Glycosylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D044502:Thymine DNA Glycosylase; C113921:mismatch-specific thymine uracil-DNA glycosylase