scholarly journals Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage

2018 ◽  
Author(s):  
Janelle Grendler ◽  
Sara Lowgren ◽  
Monique Mills ◽  
Vicki P. Losick
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Cell Division ◽  
Tissue Repair ◽  
Wound Repair ◽  
Mitotic Cell ◽  
S Phase ◽  
Polyploid Cell ◽  
Mitotic Cell Cycle ◽  
Viable Option

AbstractTissue repair requires either polyploid cell growth or cell division, but the molecular mechanism promoting polyploidy and limiting proliferation remains poorly understood. Here we find that injury to the adult Drosophila epithelium causes cells to enter the endocycle through the activation of Yorkie dependent genes (myc, e2f1, or cycE). Myc is even sufficient to induce the endocycle in the post-mitotic epithelium. As result, epithelial cells enter S phase but mitosis is blocked by inhibition of mitotic gene expression. The mitotic cell cycle program can be activated by simultaneously expressing the mitotic activator, Stg, while genetically depleting fzr. However, forcing cells to undergo mitosis is detrimental to wound repair as the adult fly epithelium accumulates DNA damage and mitotic errors ensue when cells are forced to proliferate. In conclusion, we find that wound-induced polyploidization enables tissue repair when cell division is not a viable option.

Induction of yeast histone genes by stimulation of stationary-phase cells

1990 ◽  
Vol 10 (12) ◽  
pp. 6356-6361
Author(s):  
M A Drebot ◽  
L M Veinot-Drebot ◽  
R A Singer ◽  
G C Johnston
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stationary Phase ◽  
Mitotic Cell ◽  
Specific Gene ◽  
Mitotic Cell Cycle ◽  
Histone Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Alpha Factor ◽  
Stimulation Of

In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that is unrelated to the mitotic cell cycle. Expression of histone genes, as assessed by Northern (RNA) analysis, was shown to increase promptly after the stimulation, brought about by fresh medium, that activates stationary-phase cells to reenter the mitotic cell cycle. The use of a yeast mutant that is conditionally blocked in the resumption of proliferation at a step that is not part of the mitotic cell cycle (M.A. Drebot, G.C. Johnston, and R.A. Singer, Proc. Natl. Acad. Sci. 84:7948, 1987) showed that this increased gene expression that occurs upon stimulation of stationary-phase cells took place in the absence of DNA synthesis and without the performance of start. This stimulation-specific gene expression was blocked by the mating pheromone alpha-factor, indicating that alpha-factor directly inhibits expression of these histone genes, independently of start.

scholarly journals Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks

2016 ◽  
Vol 113 (26) ◽  
pp. E3676-E3685 ◽  
Author(s):  
Nicholas A. Willis ◽  
Chunshui Zhou ◽  
Andrew E. H. Elia ◽  
Johanne M. Murray ◽  
Antony M. Carr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Replication ◽  
Fission Yeast ◽  
Dna Damage Response ◽  
Cellular Response ◽  
Genome Stability ◽  
Biological Significance ◽  
S Phase ◽  
Damage Response

The cellular response to DNA damage during S-phase regulates a complicated network of processes, including cell-cycle progression, gene expression, DNA replication kinetics, and DNA repair. In fission yeast, this S-phase DNA damage response (DDR) is coordinated by two protein kinases: Rad3, the ortholog of mammalian ATR, and Cds1, the ortholog of mammalian Chk2. Although several critical downstream targets of Rad3 and Cds1 have been identified, most of their presumed targets are unknown, including the targets responsible for regulating replication kinetics and coordinating replication and repair. To characterize targets of the S-phase DDR, we identified proteins phosphorylated in response to methyl methanesulfonate (MMS)-induced S-phase DNA damage in wild-type, rad3∆, and cds1∆ cells by proteome-wide mass spectrometry. We found a broad range of S-phase–specific DDR targets involved in gene expression, stress response, regulation of mitosis and cytokinesis, and DNA replication and repair. These targets are highly enriched for proteins required for viability in response to MMS, indicating their biological significance. Furthermore, the regulation of these proteins is similar in fission and budding yeast, across 300 My of evolution, demonstrating a deep conservation of S-phase DDR targets and suggesting that these targets may be critical for maintaining genome stability in response to S-phase DNA damage across eukaryotes.

scholarly journals Evolutionary repair: changes in multiple functional modules allow meiotic cohesin to support mitosis

2019 ◽  
Author(s):  
Yu-Ying Phoebe Hsieh ◽  
Vasso Makrantoni ◽  
Daniel Robertson ◽  
Adèle L Marston ◽  
Andrew W Murray
Keyword(s):  
Cell Cycle ◽  
Mitotic Cell ◽  
S Phase ◽  
Genome Replication ◽  
Mitotic Cell Cycle ◽  
Functional Modules ◽  
Cell Cycle Regulators ◽  
Cellular Functions ◽  
Biochemical Activity ◽  
Sister Chromosome

AbstractDifferent members of the same protein family often perform distinct cellular functions. How much are these differing functions due to changes in a protein’s biochemical activity versus changes in other proteins? We asked how the budding yeast, Saccharomyces cerevisiae, evolves when forced to use the meiosis-specific kleisin, Rec8, instead of the mitotic kleisin, Scc1, during the mitotic cell cycle. This perturbation impairs sister chromosome linkage and reduces reproductive fitness by 45%. We evolved 15 populations for 1750 generations, substantially increasing their fitness, and analyzed their genotypes and phenotypes. We found no mutations in Rec8, but many populations had mutations in the transcriptional mediator complex, cohesin-related genes, and cell cycle regulators that induce S phase. These mutations improve sister chromosome cohesion and slow genome replication in Rec8-expressing cells. We conclude that changes in known and novel partners allow proteins to improve their ability to perform new functions.

scholarly journals Integrative analyses of gene expression profile reveal potential crucial roles of mitotic cell cycle and microtubule cytoskeleton in pulmonary artery hypertension

2020 ◽  
Author(s):  
Jing Luo ◽  
Zhenwei Liu ◽  
Chenlu Li ◽  
Ruochen Wang ◽  
Jinxia Fang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Mitotic Cell ◽  
Mitotic Cell Cycle ◽  
Public Database ◽  
Hub Genes ◽  
Microtubule Cytoskeleton ◽  
Integrative Analyses

Abstract Background: Pulmonary arterial hypertension (PAH) is a life-threatening condition that gets worse over time. Despite advances in the development of strategies for treating PAH, prognosis of the disease remains unsatisfactory, especially for advanced PAH. The aim of this study was to explore potential crucial genes and pathways associated with PAH based on integrative analyses of gene expression and shed light on the identification of biomarker for PAH. Results: Gene expression profile of pulmonary tissues from 27 PAH patients and 22 normal controls were downloaded from public database (GSE53408 and GSE113439). A total of 521 differentially expressed genes (DEGs), including 432 up-regulated DEGs and 89 down-regulated DEGs were identified using “limma” package in R. Functional enrichment analysis showed that these DEGs were mainly enriched in mitotic cell cycle process, mitotic cell cycle and microtubule cytoskeleton organization. Moreover, five key genes (CDK1, SMC2, SMC4, KIF23, and CENPE) were identified based on the comprehensive evaluation of protein-protein interaction (PPI) network analysis, modular analysis and cytohubba’s analysis, then further validated in another transcriptomic data set associated with PAH from public database (GSE33463). Furthermore, these hub genes were mainly enriched in promoting mitotic cell cycle process, which may be closely associated with the pathogenesis of PAH. We also found that the predicted micro-RNAs (miRNAs) targeting these hub genes were found to be enriched in TGF-β and Hippo signaling pathway. Conclusion:These findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.

scholarly journals Pachytene arrest and other meiotic effects of the start mutations in Saccharomyces cerevisiae.

Genetics ◽  
1989 ◽  
Vol 123 (1) ◽  
pp. 29-43 ◽  
Author(s):  
E O Shuster ◽  
B Byers
Keyword(s):  
Cell Division ◽  
Nuclear Division ◽  
Spindle Pole Body ◽  
Mitotic Cell ◽  
Spindle Pole ◽  
Mitotic Cell Cycle ◽  
Chromosomal Dna ◽  
Pole Body ◽  
Vegetative Cycle

Abstract Mutations in the Start class of cell division cycle genes (CDC28, CDC36 and CDC39) define the point in the G1 phase of the vegetative cycle at which the cell becomes committed to completing another round of cell division. Genetic, cytological and biochemical data demonstrate that these mutations cause meiotic cells to become arrested at pachytene following completion of both chromosomal DNA replication and spindle pole body (SPB) duplication. In contrast these mutations have previously been found to cause arrest of the mitotic cell cycle prior to either of these landmark events, so the role of the Start genes in these events during vegetative growth must be indirect. Our observations are consistent with the hypothesis that CDC28, CDC36 and CDC39 are required for irreversible commitment to nuclear division in both the mitotic and meiotic pathways. CDC28 was additionally found to be required for the SPB separation that precedes spindle formation in preparation for the second meiotic division. Cytological and genetic analyses of this requirement revealed both that such separation may fail independently at either SPB and that ascospore formation can proceed independently of SPB separation.

Characterization of the fission yeast cdc10+ protein that is required for commitment to the cell cycle

1989 ◽  
Vol 92 (1) ◽  
pp. 51-56 ◽  
Author(s):  
V. Simanis ◽  
P. Nurse
Keyword(s):  
Cell Cycle ◽  
Mrna Level ◽  
Apparent Molecular Weight ◽  
Mitotic Cell ◽  
Protein Product ◽  
S Phase ◽  
Mitotic Cell Cycle ◽  
State Changes ◽  
Beta Galactosidase

We have used antiserum raised against a beta-galactosidase-cdc10+ fusion protein to identify the protein product of the cdc10+ start gene of Schizosaccharomyces pombe. This gene is required for progress through the G1 phase of the cell cycle and for activating processes such as the increase in histone mRNA level in preparation for S phase. The protein has an apparent molecular weight of 87,000 and is phosphorylated on multiple serine residues. The protein remains phosphorylated throughout the mitotic cell cycle and shows no significant steady-state changes in level. The antiserum has also detected a protein similar in size to p87cdc10 in human cells.

scholarly journals A Meiosis-Specific Cyclin Regulated by Splicing Is Required for Proper Progression through Meiosis

2005 ◽  
Vol 25 (15) ◽  
pp. 6330-6337 ◽  
Author(s):  
Jordi Malapeira ◽  
Alberto Moldón ◽  
Elena Hidalgo ◽  
Gerald R. Smith ◽  
Paul Nurse ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Chromosome Segregation ◽  
Mitotic Cycle ◽  
Mitotic Cell ◽  
S Phase ◽  
Mitotic Cell Cycle ◽  
Meiotic Cell ◽  
Cyclin Dependent Kinases ◽  
Negative Factor

ABSTRACT The meiotic cell cycle is modified from the mitotic cell cycle by having a premeiotic S phase which leads to high levels of recombination, a reductional pattern of chromosome segregation at the first division, and a second division with no intervening DNA synthesis. Cyclin-dependent kinases are essential for progression through the meiotic cell cycle, as for the mitotic cycle. Here we show that a fission yeast cyclin, Rem1, is present only during meiosis. Cells lacking Rem1 have impaired meiotic recombination, and Rem1 is required for premeiotic DNA synthesis when Cig2 is not present. rem1 expression is regulated at the level of both transcription and splicing, with Mei4 as a positive and Cig2 a negative factor of rem1 splicing. This regulation ensures the timely appearance of the different cyclins during meiosis, which is required for the proper progression through the meiotic cell cycle. We propose that the meiosis-specific B-type cyclin Rem1 has a central role in bringing about progression through meiosis.

scholarly journals Differential requirements for DNA replication in the activation of mitotic checkpoints in Saccharomyces cerevisiae.

1997 ◽  
Vol 17 (6) ◽  
pp. 3315-3322 ◽  
Author(s):  
P A Tavormina ◽  
Y Wang ◽  
D J Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Gamma Irradiation ◽  
Chromosome Segregation ◽  
Mitotic Checkpoint ◽  
S Phase ◽  
Temperature Sensitive ◽  
Dna Metabolism

Checkpoints prevent inaccurate chromosome segregation by inhibiting cell division when errors in mitotic processes are encountered. We used a temperature-sensitive mutation, dbf4, to examine the requirement for DNA replication in establishing mitotic checkpoint arrest. We used gamma-irradiation to induce DNA damage and hydroxyurea to limit deoxyribonucleotides in cells deprived of DBF4 function to investigate the requirement for DNA replication in DNA-responsive checkpoints. In the absence of DNA replication, mitosis was not inhibited by these treatments, which normally activate the DNA damage and DNA replication checkpoints. Our results support a model that indicates that the assembly of replication structures is critical for cells to respond to defects in DNA metabolism. We show that activating the spindle checkpoint with nocodazole does not require prior progression through S phase but does require a stable kinetochore.

Chromosome Studies on Polyploid Cell Strains ofChinese HamsterIV: Duration of the Mitotic Cell Cycle

Caryologia ◽  
1972 ◽  
Vol 25 (3) ◽  
pp. 365-371 ◽  
Author(s):  
F. Palitti ◽  
A. Rocchi ◽  
A. Mercanti ◽  
G. Olivieri
Keyword(s):  
Cell Cycle ◽  
Mitotic Cell ◽  
Polyploid Cell ◽  
Mitotic Cell Cycle ◽  
Cell Strains
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