The budding index of Saccharomyces cerevisiae deletion strains identifies genes important for cell cycle progression

Zettel, Michael F.; Garza, Lindsay R.; Cass, Andrea M.; Myhre, Rachel A.; Haizlip, Lucy A.; Osadebe, Shirley N.; Sudimack, Daniel; Pathak, Ritu; Stone, Thomas L.; Polymenis, Michael

doi:10.1016/s0378-1097(03)00384-7

Cited by 30 publications

(24 citation statements)

References 7 publications

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“…The aberrant cell morphology seen is consistent with protracted checkpoint activation or uncoupling of the morphology checkpoint from cell cycle delay caused by DNA damage during DNA replication or defects in DNA replication (56,64,73,74). Mutations affecting HR, including sister chromatid HR and processing of HR intermediates (rad52⌬, mre11⌬, rad50⌬, xrs2⌬, esc2⌬, and mph1⌬) caused aberrant morphology when combined with the rnh203⌬ mutation.…”

Section: Discussionmentioning

confidence: 58%

“…The cell cycle distribution was followed using the budding index, which uses the bud morphology of normal log-phase cells to identify cells in G 1 phase (no bud), S phase (small bud), and G 2 /M phase (large bud). We also counted cells with aberrant morphology, which typically consist of cells with grossly elongated or multiple buds and have been observed in strains with alterations in the timing of cell cycle transitions, DNA replication defects, and uncoupling of replication defects from checkpoint responses (56,64,73,74). We observed decreased proportions of G 1 -and S-phase cells, along with an increased fraction of cells with aberrant morphologies in strains where the rnh203⌬ mutation was combined with the asf1⌬, esc2⌬, mgs1⌬, mph1⌬, mre11⌬, rad50⌬, rad52⌬, or xrs2⌬ mutation ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

et al. 2014

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Errors during DNA replication are one likely cause of gross chromosomal rearrangements (GCRs). Here, we analyze the role of RNase H2, which functions to process Okazaki fragments, degrade transcription intermediates, and repair misincorporated ribonucleotides, in preventing genome instability. The results demonstrate that rnh203 mutations result in a weak mutator phenotype and cause growth defects and synergistic increases in GCR rates when combined with mutations affecting other DNA metabolism pathways, including homologous recombination (HR), sister chromatid HR, resolution of branched HR intermediates, postreplication repair, sumoylation in response to DNA damage, and chromatin assembly. In some cases, a mutation in RAD51 or TOP1 suppressed the increased GCR rates and/or the growth defects of rnh203⌬ double mutants. This analysis suggests that cells with RNase H2 defects have increased levels of DNA damage and depend on other pathways of DNA metabolism to overcome the deleterious effects of this DNA damage.

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Section: Discussionmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

et al. 2014

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“…3C and D; Table 1). TOS9, which has more recently been referred to as EAP2 in C. albicans (27), has homologs in Schizosaccharomyces pombe (22) and S. cerevisiae (50,51). These homologs, referred to in both strains as TOS9, have been implicated in mating, gluconate transport, endoplasmic reticulum (ER) regulation, budding, and cell adhesion.…”

Section: Resultsmentioning

confidence: 99%

TOS9 Regulates White-Opaque Switching in Candida albicans

et al. 2006

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In Candida albicans, the a1-␣2 complex represses white-opaque switching, as well as mating. Based upon the assumption that the a1-␣2 corepressor complex binds to the gene that regulates white-opaque switching, a chromatin immunoprecipitation-microarray analysis strategy was used to identify 52 genes that bound to the complex. One of these genes, TOS9, exhibited an expression pattern consistent with a "master switch gene." TOS9 was only expressed in opaque cells, and its gene product, Tos9p, localized to the nucleus. Deletion of the gene blocked cells in the white phase, misexpression in the white phase caused stable mass conversion of cells to the opaque state, and misexpression blocked temperature-induced mass conversion from the opaque state to the white state. A model was developed for the regulation of spontaneous switching between the opaque state and the white state that includes stochastic changes of Tos9p levels above and below a threshold that induce changes in the chromatin state of an as-yet-unidentified switching locus. TOS9 has also been referred to as EAP2 and WOR1.White-opaque switching was first observed in a strain of Candida albicans isolated from a fatal bloodstream infection (40). The switch affected the cellular phenotype (1, 41, 42), gene expression (24), and a variety of putative virulence traits (40, 41). It also conferred the capacity to colonize skin (23). An early analysis of clinical strains performed in 1986, however, revealed that only 8% underwent the switch (D. R. Soll, unpublished observation; 44). This observation was enigmatic, since all strains of C. albicans possessed opaque state-specific genes (33). In 2002, Miller and Johnson (31) provided not only an explanation for this enigma but also a role for the whiteopaque transition. They found that while an a/␣ laboratory strain could not switch, MTLa1 and MTL␣2 deletion derivatives of that strain, which were ␣ and a, respectively, could. They demonstrated that switching in the a/␣ strain was repressed by the a1-␣2 complex, the same complex that repressed mating (31). Their results suggested that in order to switch, natural strains, which are predominantly a/␣ (26,30,48), first had to undergo homozygosis to a/a or ␣/␣. Lockhart et al. (30) generalized this observation by demonstrating that while natural a/␣ strains did not undergo white-opaque switching, spontaneously generated MTL-homozygous offspring and natural MTL-homozygous strains did switch. Miller and Johnson (31) further demonstrated that in order to mate, the a and ␣ strains they derived by deleting MTL␣2 and MTLa1, respectively, first had to switch from white to opaque. Lockhart et al. (29) generalized this observation by demonstrating that only natural a/a and ␣/␣ strains that expressed the opaque phenotype could mate. The white-opaque transition, therefore, was an essential and unique step in the C. albicans mating process (3,42,43).In spite of the fundamental role white-opaque switching plays in mating, very little is known about the molecular mechanisms that re...

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“…GID8 and DCR2 overexpression may alter cell cycle progression either by directly shortening the G 1 phase, which leads to a high budding index due to a compensatory expansion of subsequent cell cycle phases, or by simply delaying mitotic progression (34). A mitotic delay can lead to a shorter G 1 phase in the next cell cycle, presumably because it allows the cells to grow and reach the critical size for initiation in the next division faster.…”

Section: Vol 3 2004mentioning

confidence: 99%

“…The percentage of budded cells (budding index) was evaluated as described previously (34). DNA content was evaluated by flow cytometry as described previously (3).…”

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Gid8p (Dcr1p) and Dcr2p Function in a Common Pathway To Promote START Completion in Saccharomyces cerevisiae

et al. 2004

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How cells determine when to initiate DNA replication is poorly understood. Here we report that in Saccharomyces cerevisiae overexpression of the dosage-dependent cell cycle regulator genes DCR2 (YLR361C) and GID8 (DCR1/YMR135C) accelerates initiation of DNA replication. Cells lacking both GID8 and DCR2 delay initiation of DNA replication. Genetic analysis suggests that Gid8p functions upstream of Dcr2p to promote cell cycle progression. DCR2 is predicted to encode a gene product with phosphoesterase activity. Consistent with these predictions, a DCR2 allele carrying a His338 point mutation, which in known protein phosphatases prevents catalysis but allows substrate binding, antagonized the function of the wild-type DCR2 allele. Finally, we report genetic interactions involving GID8, DCR2, and CLN3 (which encodes a G 1 cyclin) or SWI4 (which encodes a transcription factor of the G 1 /S transcription program). Our findings identify two gene products with a probable regulatory role in the timing of initiation of cell division.

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The budding index of Saccharomyces cerevisiae deletion strains identifies genes important for cell cycle progression

Cited by 30 publications

References 7 publications

A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

TOS9 Regulates White-Opaque Switching in Candida albicans

Gid8p (Dcr1p) and Dcr2p Function in a Common Pathway To Promote START Completion in Saccharomyces cerevisiae

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