Regulation of Kinetochore Orientation During Meiosis in Yeast

• Applicant: Dr. Wolfgang Zachariae
• Subject Area: Cell Biology
• Term: from 2009 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 116489545

Meiosis differs from mitosis in that DNA replication is followed by a division that halves the number of chromosomes by segregating homologous chromosomes but not sister chromatids. Disjunction of maternal from paternal centromeres depends on the attachment of sister kinetochores to microtubules emanating form the same spindle pole. In budding yeast, monopolar attachment depends on the assembly of the monopolin complex and its recruitment to kinetochores. How monopolin is regulated and how it controls kinetochore orientation is unclear. We found that monopolin’s localisation at kinetochores depends on two evolutionary conserved enzymes: the Dbf4-dependent Cdc7 kinase and the polo-like kinase Cdc5. These kinases bind to each other and both are essential to phosphorylate the monopolin subunit Lrs4. We will investigate how the two kinases collaborate to phosphorylate Lrs4 and how this modification leads to kinetochore localisation of monopolin. Furthermore, we will identify monoplin’s binding partner in the kinetochore. These studies should provide insight into the mechanism of monopolar attachment, one of the key features of meiosis.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1384: Mechanisms of Genome Haploidisation