Assembly and function of Drosophila melanogaster centromeric chromatin during meiosis and development. (360G-Wellcome-100105_Z_12_Z)

Centromeres are key regions of eukaryotic chromosomes that ensure proper chromosome segregation at cell division. In most eukaryotes, centromere identity is defined epigenetically by the presence of a centromere-specific histone variant CenH3. How CenH3 is incorporated and reproducibly propagated during the cell cycle is key to understanding this essential epigenetic mechanism. Improper regulation of CenH3 assembly leads to hallmarks of cancer including the formation of extra centromeres, aberra nt segregation of chromosomes and aneuploidy. Recent studies in single cell eukaryotes or cultured cells have identified molecules critical for CenH3 assembly during the mitotic cell cycle, paving the way for investigations into the mechanisms that specify centromere identity, function and regulation in animals. Meiosis is an essential part of the reproductive cycle and chromosome segregation defects result in aneuploid eggs, sperm and resulting zygotes. However, in contrast to mitosis, the func tional requirements, cell cycle timing and regulation of CenH3 assembly in the specialised meiotic divisions are largely unknown. This proposal aims investigate the function and timing of CenH3 assembly during meiosis and early development in Drosophila melanogaster. A major goal is to uncover the contribution of centromeric chromatin to the maintenance of genome stability in meiotic and mitotic cells in multi-cellular animals.