Cejka
Fakultäten » Medizinische Fakultät » Molekulare Krebsforschung, Institut für » Prof. Dr. Petr Cejka » Cejka
Current research project
| Title / Titel | Processing of DNA ends with modified chemistry | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | One of the most toxic forms of DNA damage are DNA double-strand breaks. It has been postulated that a single double-strand break in a cell is lethal if left unrepaired. Strand breaks may form either directly upon ionizing radiation, treatment with drugs targeting topoisomerases (such as some chemotherapeutics) or indirectly when DNA replication process encounters DNA adducts or strand discontinuities. Homologous recombination is one of the principal pathways that has evolved to repair DNA double-strand breaks. The initial step in the repair mechanism is the nucleolytic processing of the double-strand DNA break to form a substrate for the strand exchange protein Rad51, which carries out the subsequent steps in homologous recombination. The processing of the double-strand breaks has been recently characterized both in vivo and in vitro with reconstituted components on DNA breaks formed by site specific nucleases. Genetic data strongly suggests that the processing mechanisms differ when DNA ends are chemically modified. This may happen frequently in vivo, as DNA ends are often covalently linked to proteins or contain oxidative DNA damage upon ionizing radiation exposure. Thus, here we would like to examine the processing of DNA ends using DNA substrates containing specific forms of DNA damage that mimic those that occur in vivo. Specifically we are interested in the nuclease activities of the Mre11-Rad50-Xrs2-Sae2 complex, which have only been poorly characterized to date, and how these functionally interact with the Exo1 and Sgs1-Dna2 pathways. |
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| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.imcr.uzh.ch/research/Cejka.html | ||
| Funding source(s) / Unterstützt durch |
Universität Zürich (position pursuing an academic career) |
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| Duration of Project / Projektdauer | Nov 2011 to Oct 2015 |