Schaer
Fakultäten » Medizinische Fakultät » Molekulare Krebsforschung, Institut für » Prof. Dr. Josef Jiricny » Schaer
Completed research project
| Title / Titel | The Role of End-Joining in DNA Double-Strand Break Repair | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | Double-strand breaks (DSB’s) in DNA constitute a significant threat to the stability of cellular genomes. They are generated through the physical impact of ionizing irradiation on DNA, but can also arise as a consequence of normal DNA metabolism (e.g. DNA replication and repair). Under certain circumstances, cells induce specific DSB’s with the purpose of reorganizing or restructuring their genome by controlled DNA recombination. In eukaryotes, two main pathways have evolved for repair of DSB’s; homologous recombination and DNA end-joining. Whereas the protein components of both pathways and, thus, most likely also the basic molecular mechanisms have been conserved throughout evolution, their relative contribution to repair of DNA DSB’s appears to vary between organisms. In mammalian cells, DNA-end-joining mediated by DNA ligase 4, XRCC4, Ku70, Ku80 and other factors seems to be the major pathway for DSB-repair, whereas yeast cells appear to preferentially employ the homology-dependent mode controlled by the RAD52 epistasis group of genes. Nevertheless, yeast possesses a highly efficient system for DSB repair by homology-independent DNA end-joining, and we have shown that this pathway depends on the yeast homologues of the mammalian DNA ligase 4, XRCC4 and the Ku proteins. Thus, yeast provides an excellent model for investigation of the different modes of eukaryotic DSB repair. Our goal is to employ this model to better understand the molecular details of DNA end-joining in particular, as well as the selectivity, coordination and physiological significance of the two alternate pathways in general. Weitere Informationen |
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| Publications / Publikationen | A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. P. Schär, G. Herrmann and T. Lindahl, (1997). Genes Dev., 11, 1912-1924.Saccharomyces cerevisiae LIF1: a function involved in DNA double-strand break repair related to mammalian XRCC4. G. Herrmann, T. Lindahl and P. Schär, (1998). EMBO J. 17, 4188-4198.Valencia, M., Bentele, M., Vaze, M.B., Herrmann, G., Kraus, E., Lee, S.E., Schar, P. and Haber, J.E. (2001) NEJ1 controls non-homologous end joining in Saccharomyces cerevisiae. Nature, 414, 666-669.Weitere Informationen | ||||||
| Keywords / Suchbegriffe | DNA repair, double-strand-break repair, DNA end-joining, DNA ligase, genetic recombination, V(D)J recombination | ||||||
| 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), Others Bonizzi Theler Stiftung |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Jan 1998 to Apr 2003 |