Thymine DNA glycosylase

Hardeland, U. and Bentele, M. and Lettieri, T. and Steinacher, R. and Jiricny, J. and Schär, P.. (2001) Thymine DNA glycosylase. Progress in nucleic acid research and molecular biology, Vol. 68. pp. 235-253.

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Official URL: http://edoc.unibas.ch/dok/A5839362

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More than 50% of colon cancer-associated mutations in the p53 tumor suppressor gene are C--<T transitions. The majority of them locate in CpG dinucleotides and are thought to have arisen through spontaneous hydrolytic deamination of 5-methylcytosine. This deamination process gives rise to G.T mispairs that need to be repaired to G.C in order to avoid C--<T mutation. Similarly, deamination of cytosine generates G.U mispairs that also produce C--<T transitions if not repaired. Restoration of both G.T and G.U mismatches was shown to be mediated by a short-patch excision repair pathway, and one principal player implicated in this process may be thymine DNA glycosylase (TDG). Human TDG was discovered as an enzyme that has the potential to specifically remove thymine and uracil bases mispaired with guanine through hydrolysis of their N-glycosidic bond, thereby generating abasic sites in DNA and initiating a base excision repair reaction. The same protein was later found to interact physically and functionally with the retinoid receptors RAR and RXR, and this implicated an unexpected function of TDG in nuclear receptor-mediated transcriptional activation of gene expression. The objective of this chapter is to put together the results of different lines of experimentation that have explored the thymine DNA glycosylase since its discovery and to critically evaluate their implications for possible physiological roles of this enzyme.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Molecular Genetics (Schär)
UniBasel Contributors:Schär, Primo Leo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Academic Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:10
Deposited On:26 Apr 2013 06:57

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