The start gene <i>CDC28</i> and the genetic stability of yeast

Devin, A. B.; Prosvirova, T. Yu.; Peshekhonov, V. T.; Chepurnaya, O. V.; Smirnova, Maksimovna; Koltovaya, N. A.; Troitskaya, E. N.; Arman, I.P.

doi:10.1002/yea.320060308

Cited by 34 publications

(29 citation statements)

References 54 publications

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“…Decreased mitotic stability is displayed by a number of cdc28 alleles (10,33). These alleles would be good candidates for mutants that have poor p40-Cdc28 interactions.…”

Section: Resultsmentioning

confidence: 99%

An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells.

1994

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The gene encoding a 40-kDa protein, previously studied as a substrate and inhibitor of the yeast cyclin-dependent protein kinase, Cdc28, has been cloned. The DNA sequence reveals that p40 is a highly charged protein of 32,187 Da with no significant homology to other proteins. Overexpression of the gene encoding p40, SIC], produces cells with an elongated bud morphology similar to that of cells with depleted levels of the CLB gene products, suggesting that p40 acts as an inhibitor of Cdc28-Clb complexes in vivo. A SIC] deletion is viable and has highly increased frequencies of broken and lost chromosomes. The deletion strain segregates out many dead cells that are primarily arrested at the G2 checkpoint in an asymmetric fashion. Only daughters and young mothers display the lethal defect, while experienced mothers appear to grow normally. These results suggest that negative regulation of Cdc28 protein kinase activity by p40 is important for faithful segregation of chromosomes to daughter cells.

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“…Decreased mitotic stability is displayed by a number of cdc28 alleles (10,33). These alleles would be good candidates for mutants that have poor p40-Cdc28 interactions.…”

Section: Resultsmentioning

confidence: 99%

An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells.

1994

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“…They began with a strain producing 50% petites and selected four mutations giving rise to a lower level of petites (Table 10) (see "No compromise" below). In further studies, Devin et al (67) found a fifth mutation, shown to be allelic to CDC28. This gene encodes the protein kinase called p34 cdc28 (p34 cdc2 in Schizosaccharomyces pombe and other eucaryotes) which, in yeasts, controls both the G 1 /S and G 2 /M transitions of the cell cycle by interactions with specific cyclins (reviewed in reference 181).…”

Section: Mtdna and The Cell Cycle: A Black Boxmentioning

confidence: 95%

Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast

Contamine

Picard

2000

Microbiol Mol Biol Rev

262

209

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SUMMARY Instability of the mitochondrial genome (mtDNA) is a general problem from yeasts to humans. However, its genetic control is not well documented except in the yeast Saccharomyces cerevisiae. From the discovery, 50 years ago, of the petite mutants by Ephrussi and his coworkers, it has been shown that more than 100 nuclear genes directly or indirectly influence the fate of the rho+ mtDNA. It is not surprising that mutations in genes involved in mtDNA metabolism (replication, repair, and recombination) can cause a complete loss of mtDNA (rho0 petites) and/or lead to truncated forms (rho−) of this genome. However, most loss-of-function mutations which increase yeast mtDNA instability act indirectly: they lie in genes controlling functions as diverse as mitochondrial translation, ATP synthase, iron homeostasis, fatty acid metabolism, mitochondrial morphology, and so on. In a few cases it has been shown that gene overexpression increases the levels of petite mutants. Mutations in other genes are lethal in the absence of a functional mtDNA and thus convert this petite-positive yeast into a petite-negative form: petite cells cannot be recovered in these genetic contexts. Most of the data are explained if one assumes that the maintenance of the rho+ genome depends on a centromere-like structure dispensable for the maintenance of rho− mtDNA and/or the function of mitochondrially encoded ATP synthase subunits, especially ATP6. In fact, the real challenge for the next 50 years will be to assemble the pieces of this puzzle by using yeast and to use complementary models, especially in strict aerobes.

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“…Even subtle changes in Cdc28 function affecting mitotic progression may impinge on chromosome stability. Indeed, mutations of several Cdc28 partners and substrates have been associated with genomic instability, whereas mutations of Cdc28 itself, such as cdc28-1N (11), cdc28-srm (12), and cdc28-5M (13), are associated with relatively nonspecific defects in chromosome segregation and/or mitotic checkpoint control. Paradoxically, current models suggest that Cdc28 and its partners are only passive effectors of the mitotic surveillance pathways (14).…”

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confidence: 99%

An Essential Function of Yeast Cyclin-dependent Kinase Cdc28 Maintains Chromosome Stability

Kitazono

Kron

2002

Journal of Biological Chemistry

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Multiple surveillance pathways maintain genomic integrity in yeast during mitosis. Although the cyclin-dependent kinase Cdc28 is a well established regulator of mitotic progression, evidence for a direct role in mitotic surveillance has been lacking. We have now implicated a conserved sequence in the Cdc28 carboxyl terminus in maintaining chromosome stability through mitosis. Six temperature-sensitive mutants were isolated via random mutagenesis of 13 carboxyl-terminal residues. These mutants identify a Cdc28 domain necessary for proper mitotic arrest in the face of kinetochore defects or microtubule inhibitors. These chromosome stabilitydefective cdc28CST mutants inappropriately continue mitosis when the mitotic spindle is disrupted at 23°C, display high rates of spontaneous chromosome loss at 30°C, and suffer catastrophic aneuploidy at 35°C. A dosage suppression screen identified Cak1, a kinase known to phosphorylate and activate Cdc28, as a specific high copy suppressor of cdc28 CST temperature sensitivity and chromosome instability. Suppression is independent of the kinase activity of Cak1, suggesting that Cak1 may bind to the carboxyl terminus to serve a non-catalytic role in assembly and/or stabilization of active Cdc28 complexes. Significantly, these studies implicate Cdc28 and Cak1 in an essential surveillance function required to maintain genetic stability through mitosis.From the onset of S phase until return to G 1 , surveillance pathways collaborate to maintain chromosome stability, monitoring completion of DNA replication and repair and determining attachment and tension in the mitotic spindle while regulating sister chromatid cohesion and mediating chromosome condensation (1). The budding yeast Saccharomyces cerevisiae offers a powerful model system with which to dissect these multiple determinants and pathways. Several genetic screens have identified genes that are implicated in chromosome stability (2, 3) and/or kinetochore function (4 -7). The yeast kinetochore is a centromere binding complex and attachment point for the plus-end of a single spindle microtubule, linking each sister chromatid to one spindle-pole body (SPB).1 Furthermore, the kinetochore is an assembly point for components of the spindle checkpoint, which mediates the dependence of mitotic progression on attachment and tension (8).The cyclin-dependent kinase Cdc28 (Cdk1 and Cdc2) is the master regulator of the yeast cell cycle (9, 10). It coordinates bud emergence, SPB duplication, and DNA replication at Start and directs spindle assembly and function in mitosis. Whereas the abundance of Cdc28 is constant, its activity is regulated by associations with cyclins, stoichiometric inhibitors, and accessory factors as well as by activating and inhibitory phosphorylations (9, 10). Even subtle changes in Cdc28 function affecting mitotic progression may impinge on chromosome stability. Indeed, mutations of several Cdc28 partners and substrates have been associated with genomic instability, whereas mutations of Cdc28 itself, such as cdc28-1...

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The start gene CDC28 and the genetic stability of yeast

Cited by 34 publications

References 54 publications

An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells.

An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells.

Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast

An Essential Function of Yeast Cyclin-dependent Kinase Cdc28 Maintains Chromosome Stability

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