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    Functional overlap among distinct G1/S inhibitory pathways allows robust G1 arrest by yeast mating pheromones

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    Authors
    Pope, Patricia A.
    Pryciak, Peter M.
    Student Authors
    Patricia A. Pope
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2013-12-01
    Keywords
    Cell Biology
    Cellular and Molecular Physiology
    Molecular Biology
    
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    Abstract
    In budding yeast, mating pheromones arrest the cell cycle in G1 phase via a pheromone-activated Cdk-inhibitor (CKI) protein, Far1. Alternate pathways must also exist, however, because deleting the cyclin CLN2 restores pheromone arrest to far1 cells. Here we probe whether these alternate pathways require the G1/S transcriptional repressors Whi5 and Stb1 or the CKI protein Sic1, whose metazoan analogues (Rb or p27) antagonize cell cycle entry. Removing Whi5 and Stb1 allows partial escape from G1 arrest in far1 cln2 cells, along with partial derepression of G1/S genes, which implies a repressor-independent route for inhibiting G1/S transcription. This route likely involves pheromone-induced degradation of Tec1, a transcriptional activator of the cyclin CLN1, because Tec1 stabilization also causes partial G1 escape in far1 cln2 cells, and this is additive with Whi5/Stb1 removal. Deleting SIC1 alone strongly disrupts Far1-independent G1 arrest, revealing that inhibition of B-type cyclin-Cdk activity can empower weak arrest pathways. Of interest, although far1 cln2 sic1 cells escaped G1 arrest, they lost viability during pheromone exposure, indicating that G1 exit is deleterious if the arrest signal remains active. Overall our findings illustrate how multiple distinct G1/S-braking mechanisms help to prevent premature cell cycle commitment and ensure a robust signal-induced G1 arrest.
    Source

    Pope PA, Pryciak PM. Functional overlap among distinct G1/S inhibitory pathways allows robust G1 arrest by yeast mating pheromones. Mol Biol Cell. 2013 Dec;24(23):3675-88. doi: 10.1091/mbc.E13-07-0373. Link to article on publisher's site

    DOI
    10.1091/mbc.E13-07-0373
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/33316
    PubMed ID
    24088572
    Related Resources
    Link to article in PubMed
    Rights

    Copyright 2013 Pope and Pryciak. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

    ae974a485f413a2113503eed53cd6c53
    10.1091/mbc.E13-07-0373
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