|Title / Titel||Biochemical analysis of the Mlh1–Mlh3 endonuclease|
|Abstract (PDF, 14 KB)|
|Summary / Zusammenfassung||In mitotically growing cells, the homologous recombination machinery is primarily involved in the repair of double-strand DNA breaks. During meiosis however, the homologous recombination has a key function to align homologous chromosomes and exchange genetic information between maternal and paternal DNA. The process is initiated by planned double-strand breaks formed by the Spo11 protein. This is followed by the processing of the broken DNA, and formation of joint molecules between primarily homologous chromosomes. A large fraction of these recombination events leads to crossovers, i.e. situations when DNA sequences between maternal and paternal chromosomes have been exchanged.
The primary pathway of meiotic recombination leading to crossover products is dependent on the Msh4-Msh5 and Mlh1-Mlh3 proteins. Msh4-Msh5 were shown to bind regions that become crossovers, and Mlh1-Mlh3 was proposed to be an endonuclease cleaving recombination intermediates including Holliday junctions downstream from Msh4-Msh5. These functions have only been inferred from genetic experiments, as these proteins have not been characterized biochemically to date. Our project is focused on the in-vitro characterization of Msh4-Msh5 and Mlh1-Mlh3 complexes on recombination intermediates. Once established, we plan to investigate the function and mechanism of action of other components of the meiotic recombination machinery.
|Project leadership and contacts /
Projektleitung und Kontakte
|Other links to external web pages||http://www.imcr.uzh.ch/research/Cejka.html|
|Funding source(s) /
|SNF (Personen- und Projektförderung)
|Duration of Project / Projektdauer||Dec 2011 to Oct 2015|