Disruption of pre-established MTOCs inheritance pattern reduces cell lifespan in budding yeast

Abstract

The mitotic division of eukaryotic cells usually ends up with an equal distribution of the replicated genome and the cellular components between the resulting cells. However, the asymmetric segregation of cellular material during cell division is an essential mechanism of cell diversification. Asymmetric divisions commonly involve the age-dependent partition of various cellular components, including specific RNAs, post-translationally modified or damaged macromolecules. By means of this asymmetric distribution of cellular components, the mother and the newly generated daughter cell can be endowed with a different potential to self-renew or differentiate into a particular cell type. The segregation of the chromosomes during mitosis is possible by their attachment to the mitotic spindle, a structure formed by microtubules that nucleate from microtubule-organizing centers (MTOCs) located at the spindle poles: the centrosomes in higher eukaryotes and the spindle pole bodies (SPBs) in budding yeast. MTOCs are inherently asymmetric, both in terms of their morphology and their age, and interestingly, they represent a highly conserved example of age-dependent segregation, since many stem cells non-randomly segregate the old and the newly-synthesized MTOC during mitosis. This asymmetric age-dependent segregation of MTOCs has been described in the Drosophila male germ line, the neocortex and radial glia cell progenitor from mice and in human neuroblastoma cell lines. Remarkably, SPB inheritance in budding yeast is also asymmetric. Specifically, the daughter cell, which guarantees the immortal lineage, inherits the old SPB, while the mother cell maintains the new SPB. However, little is known about how pre-established MTOC inheritance patterns are generated and, more importantly, about the biological function of this asymmetry. We have explored the consequences of disrupting a pre-established MTOC inheritance pattern, and our results show that SPB asymmetric inheritance is necessary to preserve the immortal lineage of new daughter cells by coupling asymmetric partitioning with the inheritance of specific age-determinants during mitosis.