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Article
Open AccessReducing Mcl-1 gene dosage induces dopaminergic neuronal loss and motor impairments in Park2 knockout mice
Mutations in the PARK2 gene are associated with early onset Parkinsonism. The Park2−/− mouse, however, does not exhibit neurodegeneration or other Parkinson’s disease (PD) phenotypes. Previously, we discovered th...
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Chapter
Cyclin E Deregulation and Genomic Instability
Precise replication of genetic material and its equal distribution to daughter cells are essential to maintain genome stability. In eukaryotes, chromosome replication and segregation are temporally uncoupled, ...
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Chapter
The ubiquitin-proteasome pathway in cell cycle control
Ubiquitin-mediated proteolysis is one of the key mechanisms underlying cell cycle control. The removal of barriers posed by accumulation of negative regulators, as well as the clearance of proteins when ...
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Article
Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes
In the budding yeast, Saccharomyces cerevisiae, a significant fraction of genes (>10%) are transcribed with cell cycle periodicity. These genes encode critical cell cycle regulators as well as proteins with no di...
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Deregulation of Cyclin E and Genomic Instability
Cyclin E deregulation has been associated with an array of human malignancies. Evidence suggests that the most critical parameter may be deregulation relative to the cell cycle, which can occur if the normal p...
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Article
Cyclin E dysregulation and chromosomal instability in endometrial cancer
Deregulation of cyclin E, an activator of cyclin-dependent kinase 2 (Cdk2), has been associated with a broad spectrum of human malignancies. Yet the mechanism linking abnormal cyclin E expression to carcinogen...
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Article
Ratchets and clocks: the cell cycle, ubiquitylation and protein turnover
Many important cell-cycle regulatory proteins are regulated post-translationally by ubiquitin-mediated proteolysis. These include both positive and negative re...
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Article
S-phase checkpoint controls mitosis via an APC-independent Cdc20p function
Cells divide with remarkable fidelity, allowing complex organisms to develop and possess longevity. Checkpoint controls contribute by ensuring that genome duplication and segregation occur without error so tha...
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Article
Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast
Cks proteins are small evolutionarily conserved proteins that interact genetically and physically with cyclin-dependent kinases. However, in spite of a large body of genetic, biochemical and structural researc...
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Article
Cell cycling? Check your brakes
If there was any pervasive theme at the Cold Spring Harbor Cell Cycle Meeting (May 15–19, 2002), it was negativity. This is clearly the age of the negative cell cycle regulator, as a large percentage of the ta...
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Article
Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line
Cyclin E, one of the activators of the cyclin-dependent kinase Cdk2, is expressed near the G1–S phase transition and is thought to be critical for the initiation of DNA replication and other S-phase functions1,2,
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Article
Mec1p regulates Pds1p levels in S phase: complex coordination of DNA replication and mitosis
Genetic evidence suggests that the securin Pds1p is the target of a late-S-phase checkpoint control. Here we show that Pds1p becomes essential once two-thirds of the genome has been replicated and that the cou...
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Article
UBA domains of DNA damage-inducible proteins interact with ubiquitin
Rad23 is a highly conserved protein involved in nucleotide excision repair (NER) that associates with the proteasome via its N-terminus. Its C-terminal ubiquitin-associated (UBA) domain is evolutionarily conserve...
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Article
Multi-step control of spindle pole body duplication by cyclin-dependent kinase
Organelles called centrosomes in metazoans or spindle pole bodies (SPBs) in yeast direct the assembly of a bipolar spindle that is essential for faithful segregation of chromosomes during mitosis. Abnormal acc...
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Article
Survivin’ cell-separation anxiety
Survivin, a cell-death inhibitor, localizes to the spindles of mitotic cells, and its absence causes both a failure in cell division and induction of cell death. Might survivin link the control of cell death w...
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Article
Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle
In yeast and somatic cells, mechanisms ensure cell-cycle events are initiated only when preceding events have been completed1. In contrast, interruption of specific cell-cycle processes in early embryonic cells o...
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Article
Deregulated cyclin E induces chromosome instability
Cyclin E, a regulatory subunit of cyclin-dependent kinase 2 (Cdk2), is an important regulator of entry into S phase in the mammalian cell cycle. In normal dividing cells, cyclin E accumulates at the G1/S-phase bo...
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Chapter
G1/S regulatory mechanisms from yeast to man
Cyclin-dependent kinases play a key role in promoting and regulating the transition from G1 to S phase in all eukaryotic organisms. The kinase activities involved are distinguished from those participating in ...
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Article
Dosage suppressors of the dominant G1 cyclin mutantCLN3-2: Identification of a yeast gene encoding a putative RNA/ssDNA binding protein
Three G1 cyclins,CLN1,CLN2, andCLN3, have been identified in the budding yeastSaccharomyces cerevisiae. G1 cyclins are essential, albeit functionally redundant, rate-limiting activators of cell cycle initiation. ...
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Article
Role for the Rho-family GTPase Cdc42 in yeast mating-pheromone signal pathway
IN the budding yeast Saccharomyces cerevisiae, the process of conjugation of haploid cells of genotype MATa and MATαto form MATa/α diploids is triggered by pheromones produced by each mating type. These pheromone...
