Cell‐cycle‐regulatory elements and the control of cell differentiation in the budding yeast

Wittenberg, Curt; Valle, Roberto La

doi:10.1002/bies.10327

Cited by 24 publications

(13 citation statements)

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“…In budding yeast, nutrient deprivation causes G1 cell cycle arrest and meiotic initiation (Honigberg and Purnapatre, 2003;Wittenberg and La Valle, 2003). Cell cycle regulators appear to play an important role in this switch, keeping the mitotic cell cycle and meiotic initiation mutually exclusive (Colomina et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

et al. 2011

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SUMMARYThe C. elegans germline provides an excellent model for analyzing the regulation of stem cell activity and the decision to differentiate and undergo meiotic development. The distal end of the adult hermaphrodite germline contains the proliferative zone, which includes a population of mitotically cycling cells and cells in meiotic S phase, followed by entry into meiotic prophase. The proliferative fate is specified by somatic distal tip cell (DTC) niche-germline GLP-1 Notch signaling through repression of the redundant GLD-1 and GLD-2 pathways that promote entry into meiosis. Here, we describe characteristics of the proliferative zone, including cell cycle kinetics and population dynamics, as well as the role of specific cell cycle factors in both cell cycle progression and the decision between the proliferative and meiotic cell fate. Mitotic cell cycle progression occurs rapidly, continuously, with little or no time spent in G1, and with cyclin E (CYE-1) levels and activity high throughout the cell cycle. In addition to driving mitotic cell cycle progression, CYE-1 and CDK-2 also play an important role in proliferative fate specification. Genetic analysis indicates that CYE-1/CDK-2 promotes the proliferative fate downstream or in parallel to the GLD-1 and GLD-2 pathways, and is important under conditions of reduced GLP-1 signaling, possibly corresponding to mitotically cycling proliferative zone cells that are displaced from the DTC niche. Furthermore, we find that GLP-1 signaling regulates a third pathway, in addition to the GLD-1 and GLD-2 pathways and also independent of CYE-1/CDK-2, to promote the proliferative fate/inhibit meiotic entry.

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Section: Introductionmentioning

confidence: 99%

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

et al. 2011

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“…In S. cerevisiae, cell-cycle arrest is often achieved by altering Cdc28p activity by mechanisms such as Cdc28p phosphorylation and the modulation of cyclin levels Reed, 1993, 1995). For example, the morphogenesis-checkpoint kinase Swe1p catalyzes inhibitory phosphorylation of Cdc28p and thus prevents entry into mitosis, leading to the formation of elongated cells (Booher et al, 1993;Wittenberg and La Valle, 2003). In addition, the DNAreplication checkpoint appears to mediate HU-induced pseudohyphal growth (Jiang and Kang, 2003).…”

Section: Introductionmentioning

confidence: 99%

Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth inCandida albicans

Shi

Wang

Zheng

et al. 2007

MBoC

119

198

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The polymorphic fungus Candida albicans switches from yeast to filamentous growth in response to a range of genotoxic insults, including inhibition of DNA synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the ribonucleotidereductase subunit Rnr2p, and DNA damage induced by methylmethane sulfonate (MMS) or UV light (UV). Deleting RAD53, which encodes a downstream effector kinase for both the DNA-replication and DNA-damage checkpoint pathways, completely abolished the filamentous growth caused by all the genotoxins tested. Deleting RAD9, which encodes a signal transducer of the DNA-damage checkpoint, specifically blocked the filamentous growth induced by MMS or UV but not that induced by HU or AC. Deleting MRC1, the counterpart of RAD9 in the DNA-replication checkpoint, impaired DNA synthesis and caused cell elongation even in the absence of external genotoxic insults. Together, the results indicate that the DNA-replication/damage checkpoints are critically required for the induction of filamentous growth by genotoxic stress. In addition, either of two mutations in the FHA1 domain of Rad53p, G65A, and N104A, nearly completely blocked the filamentous-growth response but had no significant deleterious effect on cell-cycle arrest. These results suggest that the FHA domain, known for its ability to bind phosphopeptides, has an important role in mediating genotoxic-stress-induced filamentous growth and that such growth is a specific, Rad53p-regulated cellular response in C. albicans. INTRODUCTIONThe polymorphic fungus Candida albicans has proven to be a very useful model for the study of cell morphogenesis (Odds, 1994;Sudbery et al., 2004;Wightman et al., 2004;Zheng et al., 2004). This organism can switch between several morphological forms including yeast, pseudohyphae, and hyphae (Berman and Sudbery, 2002;Sudbery et al., 2004). The yeast-hypha transition has attracted much attention because of its established importance for infection and virulence (Csank et al., 1997;Lo et al., 1997;Gale et al., 1998;Gow et al., 2002;Zheng et al., 2004). Several signal-transduction pathways are known to play roles in growth-form selection (Liu, 2001;Berman and Sudbery, 2002). The cAMPprotein kinase A (PKA) pathway has a key role, because blocking it abolishes true hyphal growth under most experimental conditions (Lo et al., 1997;Stoldt et al., 1997;Rocha et al., 2001). Another important pathway contains a MAPkinase cascade that seems to have a more important role in regulating pseudohyphal than true hyphal growth (Liu et al., 1994). The two pathways control the transcription factors Efg1p and Cph1p, respectively, which activate the expression of hypha-specific genes for a suite of infection-related functions (Lane et al., 2001).A diverse range of environmental stimuli can induce C. albicans hyphal or pseudohyphal growth, such as serum, neutral pH, appropriate temperature, certain amino acids and sugars, and some synthetic growth media (Ernst, 2000;Sudbery et al., 2004). These conditions more-or-less mimic certain host c...

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“…When these events are impaired, the checkpoints temporarily arrest cell cycle progression to provide time for repairing damage and correcting mistakes. In S. cerevisiae, defective bud construction activates the Swe1-mediated morphogenesis checkpoint to temporarily arrest cell cycle progression, leading to bud elongation (11,50). Several DNA damage/replication checkpoint proteins, such as Mec1 and Rad53, have been found to be involved in the filamentous growth induced by DNA replication stress (25,42).…”

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confidence: 99%

Protein Phosphatase Pph3 and Its Regulatory Subunit Psy2 Regulate Rad53 Dephosphorylation and Cell Morphogenesis during Recovery from DNA Damage in Candida albicans

Sun

Wang

et al. 2011

Eukaryot Cell

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The ability of the pathogenic fungus Candida albicans to switch cellular morphologies is important for infection and virulence. Recent studies have revealed that C. albicans yeast cells can switch to filamentous growth under genotoxic stress in a manner dependent on the DNA replication/damage checkpoint. Here, we have investigated the functions of Pph3 (orf19.4378) and Psy2 (orf19.3685), whose orthologues in Saccharomyces cerevisiae mediate the dephosphorylation of the DNA damage checkpoint kinase Rad53 and the histone variant H2AX during recovery from DNA damage. Deleting PPH3 or PSY2 causes hypersensitivity to DNAdamaging agents, including cisplatin, methylmethane sulfonate (MMS), and UV light. In addition, pph3⌬ and psy2⌬ cells exhibit strong filamentous growth under genotoxic stress. Flow cytometry analysis shows that the mutant cells have lost the ability to adapt to genotoxic stress and remain arrested even after the stress is withdrawn. Furthermore, we show that Pph3 and Psy2 are required for the dephosphorylation of Rad53, but not H2AX, during DNA damage recovery. Taken together, these results show that C. albicans Pph3 and Psy2 have important roles in mediating genotoxin-induced filamentous growth and regulating Rad53 dephosphorylation.

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Cell‐cycle‐regulatory elements and the control of cell differentiation in the budding yeast

Cited by 24 publications

References 86 publications

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth inCandida albicans

Protein Phosphatase Pph3 and Its Regulatory Subunit Psy2 Regulate Rad53 Dephosphorylation and Cell Morphogenesis during Recovery from DNA Damage in Candida albicans

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