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A memory system of negative polarity cues prevents replicative aging

Summary Cdc42 is a highly conserved master regulator of cell polarity. Here, we investigated the mechanism by which yeast cells never re-establish polarity at cortical sites (cytokinesis remnants [CRMs]) that have previously supported Cdc42-mediated growth as a paradigm to mechanistically understand...

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Main Authors: Meitinger, Franz (Author) , Khmelinskii, Anton (Author) , Kurtulmus, Bahtiyar (Author) , Palani, Saravanan (Author) , Knop, Michael (Author) , Pereira, Gislene (Author)
Format: Article (Journal)
Language:English
Published: November 20, 2014
In: Cell
Year: 2014, Volume: 159, Issue: 5, Pages: 1056-1069
ISSN:1097-4172
DOI:10.1016/j.cell.2014.10.014
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.cell.2014.10.014
Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S0092867414013026
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Author Notes:Franz Meitinger, Anton Khmelinskii, Sandrine Morlot, Bahtiyar Kurtulmus, Saravanan Palani, Amparo Andres-Pons, Birgit Hub, Michael Knop, Gilles Charvin, and Gislene Pereira

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520 |a Summary Cdc42 is a highly conserved master regulator of cell polarity. Here, we investigated the mechanism by which yeast cells never re-establish polarity at cortical sites (cytokinesis remnants [CRMs]) that have previously supported Cdc42-mediated growth as a paradigm to mechanistically understand how Cdc42-inhibitory polarity cues are established. We revealed a two-step mechanism of loading the Cdc42 antagonist Nba1 into CRMs to mark these compartments as refractory for a second round of Cdc42 activation. Our data indicate that Nba1 together with a cortically tethered adaptor protein confers memory of previous polarization events to translate this spatial legacy into a biochemical signal that ensures the local singularity of Cdc42 activation. “Memory loss” mutants that repeatedly use the same polarity site over multiple generations display nuclear segregation defects and a shorter lifespan. Our work thus established CRMs as negative polarity cues that prevent Cdc42 reactivation to sustain the fitness of replicating cells. 
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