Ghavidel A~Harkness TAA, 2015

Pubmed ID 26247883
Title A Genome Scale Screen for Mutants with Delayed Exit from Mitosis: Ire1-Independent Induction of Autophagy Integrates ER Homeostasis into Mitotic Lifespan.
Authors Ata Ghavidel, Kunal Baxi, Vladimir Ignatchenko, Martin Prusinkiewicz, Terra G Arnason, Thomas Kislinger, Carlos E Carvalho, Troy A A Harkness
Abstract Proliferating eukaryotic cells undergo a finite number of cell divisions before irreversibly exiting mitosis. Yet pathways that normally limit the number of cell divisions remain poorly characterized. Here we describe a screen of a collection of 3762 single gene mutants in the yeast Saccharomyces cerevisiae, accounting for 2/3 of annotated yeast ORFs, to search for mutants that undergo an atypically high number of cell divisions. Many of the potential longevity genes map to cellular processes not previously implicated in mitotic senescence, suggesting that regulatory mechanisms governing mitotic exit may be broader than currently anticipated. We focused on an ER-Golgi gene cluster isolated in this screen to determine how these ubiquitous organelles integrate into mitotic longevity. We report that a chronic increase in ER protein load signals an expansion in the assembly of autophagosomes in an Ire1-independent manner, accelerates trafficking of high molecular weight protein aggregates from the cytoplasm to the vacuoles, and leads to a profound enhancement of daughter cell production. We demonstrate that this catabolic network is evolutionarily conserved, as it also extends reproductive lifespan in the nematode Caenorhabditis elegans. Our data provide evidence that catabolism of protein aggregates, a natural byproduct of high protein synthesis and turn over in dividing cells, is among the drivers of mitotic longevity in eukaryotes.
Citation PLoS Genet. 2015; 11:e1005429

Datasets

Download the list of datasets
Papers Phenotype Conditions Collection Tested mutants Data Details
Ghavidel A~Harkness TAA, 2015 replicative lifespan (relative abundance in pool counterselected for derepression of HML locus) YPD [standard], time [6 d] hap a ~3,762 Discrete
Ghavidel A~Harkness TAA, 2015 replicative lifespan (relative abundance in pool counterselected for derepression of HML locus) time [16 d], YPD [standard] hap a ~3,762 Discrete

Curation history

Data

Sept. 12, 2016 Data requested.
April 25, 2017 Data requested.
June 23, 2017 Data to load.
July 11, 2017 Data loaded.

Tested strains

Sept. 12, 2016 Tested strains requested.
April 25, 2017 Tested strains requested.
June 23, 2017 Tested strains abandoned.