scholarly journals Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Rati Verma ◽  
Robert S Oania ◽  
Natalie J Kolawa ◽  
Raymond J Deshaies
Keyword(s):  
Budding Yeast ◽  
Human Diseases ◽  
Nascent Chain

Ubiquitin-dependent proteolysis can initiate at ribosomes for myriad reasons including misfolding of a nascent chain or stalling of the ribosome during translation of mRNA. Clearance of a stalled complex is required to recycle the ribosome for future use. Here we show that the ubiquitin (Ub) pathway segregase Cdc48/p97 and its adaptors Ufd1-Npl4 participate in ribosome-associated degradation (RAD) by mediating the clearance of ubiquitinated, tRNA-linked nascent peptides from ribosomes. Through characterization of both endogenously-generated and heterologous model substrates for the RAD pathway, we conclude that budding yeast Cdc48 functions downstream of the Ub ligases Ltn1 and Ubr1 to release nascent proteins from the ribosome so that they can be degraded by the proteasome. Defective RAD could contribute to the pathophysiology of human diseases caused by mutations in p97.

scholarly journals Isolation and characterization of a gene (CBF2) specifying a protein component of the budding yeast kinetochore.

1993 ◽  
Vol 121 (3) ◽  
pp. 513-519 ◽  
Author(s):  
W Jiang ◽  
J Lechner ◽  
J Carbon
Keyword(s):  
Molecular Motors ◽  
Cell Biology ◽  
Budding Yeast ◽  
Isolation And Characterization ◽  
Sequence Homologies ◽  
Binding Factor ◽  
Microtubule Motor

We have cloned and determined the nucleotide sequence of the gene (CBF2) specifying the large (110 kD) subunit of the 240-kD multisubunit yeast centromere binding factor CBF3, which binds selectively in vitro to yeast centromere DNA and contains a minus end-directed microtubule motor activity. The deduced amino acid sequence of CBF2p shows no sequence homologies with known molecular motors, although a consensus nucleotide binding site is present. The CBF2 gene is essential for viability of yeast and is identical to NDC10, in which a conditional mutation leads to a defect in chromosome segregation (Goh, P.-Y., and J. V. Kilmartin, in this issue of The Journal of Cell Biology). The combined in vitro and in vivo evidence indicate that CBF2p is a key component of the budding yeast kinetochore.

scholarly journals Quantitative Characterization of a Mitotic Cyclin Threshold Regulating Exit from Mitosis

2005 ◽  
Vol 16 (5) ◽  
pp. 2129-2138 ◽  
Author(s):  
Frederick R. Cross ◽  
Lea Schroeder ◽  
Martin Kruse ◽  
Katherine C. Chen
Keyword(s):  
Cell Cycle ◽  
Budding Yeast ◽  
Cell Cycle Control ◽  
Predictive Ability ◽  
Eukaryotic Cell ◽  
Model Predictions ◽  
Mitotic Cyclin ◽  
Constitutive Overexpression

Regulation of cyclin abundance is central to eukaryotic cell cycle control. Strong overexpression of mitotic cyclins is known to lock the system in mitosis, but the quantitative behavior of the control system as this threshold is approached has only been characterized in the in vitro Xenopus extract system. Here, we quantitate the threshold for mitotic block in budding yeast caused by constitutive overexpression of the mitotic cyclin Clb2. Near this threshold, the system displays marked loss of robustness, in that loss or even heterozygosity for some regulators becomes deleterious or lethal, even though complete loss of these regulators is tolerated at normal cyclin expression levels. Recently, we presented a quantitative kinetic model of the budding yeast cell cycle. Here, we use this model to generate biochemical predictions for Clb2 levels, asynchronous as well as through the cell cycle, as the Clb2 overexpression threshold is approached. The model predictions compare well with biochemical data, even though no data of this type were available during model generation. The loss of robustness of the Clb2 overexpressing system is also predicted by the model. These results provide strong confirmation of the model's predictive ability.

Characterization of G1 and Mitotic Cyclins of Budding Yeast

1991 ◽  
Vol 56 (0) ◽  
pp. 21-32 ◽  
Author(s):  
M. Tyers ◽  
I. Fitch ◽  
G. Tokiwa ◽  
C. Dahmann ◽  
R. Nash ◽  
...  
Keyword(s):  
Budding Yeast

scholarly journals A brief history of TOR

2011 ◽  
Vol 39 (2) ◽  
pp. 437-442 ◽  
Author(s):  
Robbie Loewith
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Antifungal Agent ◽  
Budding Yeast ◽  
Intermediary Metabolism ◽  
Molecular Pathways ◽  
Central Importance ◽  
Yeast Saccharomyces Cerevisiae ◽  
Initial Characterization ◽  
History Of

The TOR (target of rapamycin) serine/threonine kinases are fascinating in that they influence many different aspects of eukaryote physiology including processes often dysregulated in disease. Beginning with the initial characterization of rapamycin as an antifungal agent, studies with yeast have contributed greatly to our understanding of the molecular pathways in which TORs operate. Recently, building on advances in quantitative MS, the rapamycin-dependent phosphoproteome in the budding yeast Saccharomyces cerevisiae was elucidated. These studies emphasize the central importance of TOR and highlight its many previously unrecognized functions. One of these, the regulation of intermediary metabolism, is discussed.

Cloning and characterization of mouse Dhm2 cDNA, a functional homolog of budding yeast SEP1

Gene ◽  
1997 ◽  
Vol 191 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Takeo Shobuike ◽  
Shoji Sugano ◽  
Teruhito Yamashita ◽  
Hideo Ikeda
Keyword(s):  
Budding Yeast ◽  
Functional Homolog

scholarly journals Characterization of Dependencies Between Growth and Division in Budding Yeast

2016 ◽  
Author(s):  
Michael B. Mayhew ◽  
Edwin S. Iversen ◽  
Alexander J. Hartemink
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Size Control ◽  
Inverse Correlation ◽  
Time Lapse ◽  
Independent Manner ◽  
Statistical Framework ◽  
Cell Variation

AbstractCell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeastSaccharomyces cerevisiae, this coordination or ‘size control’ appears as an inverse correlation between cell size and the rate of cell-cycle progression, routinely observed in G1prior to cell division commitment. Beyond this point, cells are presumed to complete S/G2/M at similar rates and in a size-independent manner. As such, studies of dependence between growth and division have focused on G1. Moreover, coordination between growth and division has commonly been analyzedwithinthe cycle of a single cell without accounting for correlations in growth and division characteristicsbetweencycles of related cells. In a comprehensive analysis of three published time-lapse microscopy datasets, we analyze both intra-and inter-cycle dependencies between growth and division, revisiting assumptions about the coordination between these two processes. Interestingly, we find evidence (1) that S/G2/M durations are systematically longer in daughters than in mothers, (2) of dependencies between S/G2/M and size at budding that echo the classical G1dependencies, and, (3) in contrast with recent bacterial studies, of negative dependencies between size at birth and size accumulated during the cell cycle. In addition, we develop a novel hierarchical model to uncover inter-cycle dependencies, and we find evidence for such dependencies in cells growing in sugar-poor environments. Our analysis highlights the need for experimentalists and modelers to account for new sources of cell-to-cell variation in growth and division, and our model provides a formal statistical framework for the continued study of dependencies between biological processes.

scholarly journals Canonical and novel non-canonical activities of the Holliday junction resolvase Yen1

2020 ◽  
Author(s):  
F. Javier Aguado ◽  
Raquel Carreira ◽  
Vanesa Hurtado-Nieves ◽  
Miguel G. Blanco
Keyword(s):  
Budding Yeast ◽  
Holliday Junction ◽  
Conformational Preference ◽  
Alternative Processing ◽  
Holliday Junction Resolvase ◽  
Replication Intermediates

ABSTRACTYen1 and GEN1 are members of the Rad2/XPG family of nucleases that were identified as the first canonical nuclear Holliday junction (HJ) resolvases in budding yeast and humans due to their ability to introduce two symmetric, coordinated incisions on opposite strands of the HJ, yielding nicked DNA products that could be readily ligated. While GEN1 has been extensively characterized in vitro, much less is known about the biochemistry of Yen1. Here, we have performed the first in-depth characterization of purified Yen1. We confirmed that Yen1 resembles GEN1 in many aspects, including range of substrates targeted, position of most incisions they produce or monomeric state in solution. However, we have also observed unexpected alternative processing of substrates, such as nicked HJs and a different conformational preference on intact HJs. Moreover, we demonstrate that Yen1 is endowed with additional nuclease activities, like a nick-specific 5’-3’ exonuclease or HJ arm-chopping that could apparently blur its classification as a canonical HJ resolvase. Despite this, we show that Yen1 fulfills the requirements of a canonical HJ resolvase and hypothesize that its wider array of nuclease activities might contribute to its function in the removal of persistent recombination or replication intermediates.

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