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Science

Title:		"Aggregation of the Whi3 protein, not loss of heterochromatin, causes sterility in old yeast cells"
Author(s):		Schlissel G; Krzyzanowski MK; Caudron F; Barral Y; Rine J;
Address:		"Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720, USA. Institute of Biochemistry, ETH Zurich, Zurich, Switzerland. King's College London, London, UK. Institute of Biochemistry, ETH Zurich, Zurich, Switzerland. yves.barral@bc.biol.ethz.ch jrine@berkeley.edu. Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720, USA. yves.barral@bc.biol.ethz.ch jrine@berkeley.edu"
Journal Title:		Science
Year:		2017
Volume:		20170316
Issue:		6330
Page Number:		1184 - 1187
DOI:		10.1126/science.aaj2103
ISSN/ISBN:		1095-9203 (Electronic) 0036-8075 (Print) 0036-8075 (Linking)
Abstract:		"In yeast, heterochromatin silencing is reported to decline in aging mother cells, causing sterility in old cells. This process is thought to reflect a decrease in the activity of the NAD(+) (oxidized nicotinamide adenine dinucleotide)-dependent deacetylase Sir2. We tested whether Sir2 becomes nonfunctional gradually or precipitously during aging. Unexpectedly, silencing of the heterochromatic HML and HMR loci was not lost during aging. Old cells could initiate a mating response; however, they were less sensitive to mating pheromone than were young cells because of age-dependent aggregation of Whi3, an RNA-binding protein controlling S-phase entry. Removing the polyglutamine domain of Whi3 restored the pheromone sensitivity of old cells. We propose that aging phenotypes previously attributed to loss of heterochromatin silencing are instead caused by aggregation of the Whi3 cell cycle regulator"
Keywords:		"Cellular Senescence/genetics/*physiology *Gene Expression Regulation, Fungal *Gene Silencing *Genes, Mating Type, Fungal Heterochromatin/*metabolism Peptides/genetics/physiology *Protein Aggregates Protein Domains/genetics/physiology RNA-Binding Proteins/;"
Notes:		"MedlineSchlissel, Gavin Krzyzanowski, Marek K Caudron, Fabrice Barral, Yves Rine, Jasper eng R01 GM031105/GM/NIGMS NIH HHS/ R37 GM031105/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2017/03/18 Science. 2017 Mar 17; 355(6330):1184-1187. doi: 10.1126/science.aaj2103. Epub 2017 Mar 16"