In this Thesis we address two important aspects of protein dynamics: protein synthesis and distribution upon cell division and dynamics of the protein degradation machinery. In Chapter 2, we present novel technology (Recombination-Induced Tag Exchange)to distinguish and simultaneously track old and new proteins. In Chapter 3 we usedthis technology to make a comprehensive analysis of the inheritance and synthesis of organelles and macromolecular complexes in budding yeast. Thereby we resolved outstanding issues in organelle synthesis and uncovered symmetrical and asymmetrical patterns of inheritance. Asymmetrical inheritance of organelles and macromolecular complexes may induce lineage differences and could be involved in cell differentiation. Next, we address two aspects of the dynamics of the protein degradation machinery that may be relevant for cellular aging: proteasome localization and degradation of the proteasome. In Chapter 4 we show that the localization of the proteasome, like its activity, may be a relevant factor in cellular aging and identify genetic factors affecting proteasome localization and longevity in budding yeast. In Chapter 5 we present data that is consistent with lysosomal degradation of damaged proteasomes, which may represent the first sketches of a quality control mechanism for the proteasome.Netherlands Proteomics CentreUBL - phd migration 201
