Schaer
Fakultäten » Medizinische Fakultät » Molekulare Krebsforschung, Institut für » Prof. Dr. Josef Jiricny » Schaer
Completed research project
| Title / Titel | Thymine DNA-Glycosylase - Antimutator and Tumour Suppressor? | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | Genomic DNA of higher eukaryotes is methylated on cytosines in the context of CG dinucleotides. Cytosine and 5-methylcytosine are subject to spontaneous hydrolytic deamination, which generates uracil/guanine (U/G) and thymine/guanine (T/G) mispairs in DNA. While both these lesions are corrected by a base excision repair mechanism, U/G repair is initiated by the abundant and ubiquitous uracil DNA-glycosyalse (UDG), while the initial step of T/G repair, namely, the removal of the mispaired thymine, is mediated by thymine DNA-glycosylase, TDG. Since the discovery of this enzyme in 1989, we have been studying the biochemistry of the repair process and the role of this protein in mutagenesis in vivo. More recent experiments showed that TDG is a member of a highly-conserved family of proteins that are found also in organisms which do not methylate cytosine. The biological role of the TDG homologues in Drosophila melanogaster and Schizosaccharomyces pombe is thus the subject of intense study in our laboratory. Weitere Informationen |
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| Publications / Publikationen | Hardeland, U., Bentele, M., Lettieri, T., Steinacher, R., Jiricny, J. and Schär, P. (2001) Thymine DNA glycosylase. In Moldave, K., Mitra, S., McCullough, A.K., Lloyd, R.S. and Wilson, S.H. (eds.), Progress in nucleic acid research and molecular biology - Base excision repair. Academic Press, San Diego, Vol. 68, pp. 235-252.Hardeland, U., Steinacher, R., Jiricny, J. and Schar, P. (2002) Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover. EMBO J, 21, 1456-1464. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11889051Hardeland, U., Bentele, M., Jiricny, J. and Schär, P. (2003) The versatile thymine DNA-glycosylase: a comparative characterization of the human, Drosophila and fission yeast orthologs. Nucleic Acids Res, 31, 2261-2271. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12711670Weitere Informationen |
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| Keywords / Suchbegriffe | DNA repair, base excision repair, TDG, DNA glycosylase, methylation, deamination, mismatch repair | ||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.imr.uzh.ch | ||||||
| Funding source(s) / Unterstützt durch |
Universität Zürich (position pursuing an academic career), SNF (Personen- und Projektförderung), Others Julius Mueller Stiftung Sussella Stiftung Association for International Cancer Research (AICR) |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Sep 1998 to Apr 2003 |