The Drosophila gene morula inhibits mitotic functions in the endo cell cycle and the mitotic cell cycle

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3543-3553 ◽  
Author(s):  
B.H. Reed ◽  
T.L. Orr-Weaver
Keyword(s):  
Cell Cycle ◽  
Mitotic Cycle ◽  
Mitotic Cell ◽  
Cyclin B ◽  
Dual Function ◽  
Nurse Cells ◽  
M Cell ◽  
Ring Gland ◽  
Dividing Cells ◽  
A Cell

In the endo cell cycle, rounds of DNA replication occur in the absence of mitosis, giving rise to polyploid or polytene cells. We show that the Drosophila morula gene is essential to maintain the absence of mitosis during the endo cycle. During oogenesis in wild-type Drosophila, nurse cells become polyploid and do not contain cyclin B protein. Nurse cells in female-sterile alleles of morula begin to become polyploid but revert to a mitotic-like state, condensing the chromosomes and forming spindles. In strong, larval lethal alleles of morula, the polytene ring gland cells also inappropriately regress into mitosis and form spindles. In addition to its role in the endo cycle, morula function is necessary for dividing cells to exit mitosis. Embryonic S-M cycles and the archetypal (G1-S-G2-M) cell cycle are both arrested in metaphase in different morula mutants. These phenotypes suggest that morula acts to block mitosis-promoting activity in both the endo cycle and at the metaphase/anaphase transition of the mitotic cycle. Consistent with this, we found cyclin B protein to be inappropriately present in morula mutant nurse cells. Thus morula serves a dual function as a cell cycle regulator that promotes exit from mitosis and maintains the absence of mitosis during the endo cycle, possibly by activating the cyclin destruction machinery.

scholarly journals Reprogramming the Cell Cycle for Endoreduplication in Rodent Trophoblast Cells

1998 ◽  
Vol 9 (4) ◽  
pp. 795-807 ◽  
Author(s):  
Alasdair MacAuley ◽  
James C. Cross ◽  
Zena Werb
Keyword(s):  
Cell Cycle ◽  
Cell Differentiation ◽  
Giant Cell ◽  
Mitotic Cycle ◽  
Mitotic Cell ◽  
Giant Cells ◽  
Cyclin B ◽  
Helix Loop Helix ◽  
Trophoblast Giant Cells ◽  
Cycle Regulation

Differentiation of trophoblast giant cells in the rodent placenta is accompanied by exit from the mitotic cell cycle and onset of endoreduplication. Commitment to giant cell differentiation is under developmental control, involving down-regulation of Id1and Id2, concomitant with up-regulation of the basic helix-loop-helix factor Hxt and acquisition of increased adhesiveness. Endoreduplication disrupts the alternation of DNA synthesis and mitosis that maintains euploid DNA content during proliferation. To determine how the mammalian endocycle is regulated, we examined the expression of the cyclins and cyclin-dependent kinases during the transition from replication to endoreduplication in the Rcho-1 rat choriocarcinoma cell line. We cultured these cells under conditions that gave relatively synchronous endoreduplication. This allowed us to study the events that occur during the transition from the mitotic cycle to the first endocycle. With giant cell differentiation, the cells switched cyclin D isoform expression from D3 to D1 and altered several checkpoint functions, acquiring a relative insensitivity to DNA-damaging agents and a coincident serum independence. The initiation of S phase during endocycles appeared to involve cycles of synthesis of cyclins E and A, and termination of S was associated with abrupt loss of cyclin A and E. Both cyclins were absent from gap phase cells, suggesting that their degradation may be necessary to allow reinitiation of the endocycle. The arrest of the mitotic cycle at the onset of endoreduplication was associated with a failure to assemble cyclin B/p34cdk1complexes during the first endocycle. In subsequent endocycles, cyclin B expression was suppressed. Together these data suggest several points at which cell cycle regulation could be targeted to shift cells from a mitotic to an endoreduplicative cycle.

Notch-Delta signaling induces a transition from mitotic cell cycle to endocycle inDrosophilafollicle cells

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4737-4746 ◽  
Author(s):  
Wu-Min Deng ◽  
Cassandra Althauser ◽  
Hannele Ruohola-Baker
Keyword(s):  
Cell Cycle ◽  
Mitotic Cycle ◽  
Notch Pathway ◽  
Follicle Cell ◽  
Delta Function ◽  
Mitotic Cell ◽  
Follicle Cells ◽  
Transcriptional Level ◽  
M Cell ◽  
Normal Transition

In many developmental processes, polyploid cells are generated by a variation of the normal cell cycle called the endocycle in which cells increase their genomic content without dividing. How the transition from the normal mitotic cycle to endocycle is regulated is poorly understood. We show that the transition from mitotic cycle to endocycle in the Drosophila follicle cell epithelium is regulated by the Notch pathway. Loss of Notch function in follicle cells or its ligand Delta function in the underlying germline disrupts the normal transition of the follicle cells from mitotic cycle to endocycle, mitotic cycling continues, leading to overproliferation of these cells. The regulation is at the transcriptional level, as Su(H), a downstream transcription factor in the pathway, is also required cell autonomously in follicle cells for proper transitioning to the endocycle. One target of Notch and Su(H) is likely to be the G2/M cell cycle regulator String, a phosphatase that activates Cdc2 by dephosphorylation. String is normally repressed in the follicle cells just before the endocycle transition, but is expressed when Notch is inactivated. Analysis of the activity of String enhancer elements in follicle cells reveals the presence of an element that promotes expression of String until just before the onset of polyploidy in wild-type follicle cells but well beyond this stage in Notch mutant follicle cells. This suggests that it may be the target of the endocycle promoting activity of the Notch pathway. A second element that is insensitive to Notch regulation promotes String expression earlier in follicle cell development, which explains why Notch, while active at both stages, represses String only at the mitotic cycle-endocycle transition.

The interplay between cyclin-B-Cdc2 kinase (MPF) and MAP kinase during maturation of oocytes

2001 ◽  
Vol 114 (2) ◽  
pp. 257-267 ◽  
Author(s):  
A. Abrieu ◽  
M. Doree ◽  
D. Fisher
Keyword(s):  
Cell Cycle ◽  
Map Kinase ◽  
Cell Cycle Progression ◽  
Mitotic Cell ◽  
Model Systems ◽  
Cyclin B ◽  
Cdc2 Kinase ◽  
Meiotic Chromosomes ◽  
Map Kinase Cascade ◽  
Kinase Cascade

Throughout oocyte maturation, and subsequently during the first mitotic cell cycle, the MAP kinase cascade and cyclin-B-Cdc2 kinase are associated with the control of cell cycle progression. Many roles have been directly or indirectly attributed to MAP kinase and its influence on cyclin-B-Cdc2 kinase in different model systems; yet a principle theme does not emerge from the published literature, some of which is apparently contradictory. Interplay between these two kinases affects the major events of meiotic maturation throughout the animal kingdom, including the suppression of DNA replication, the segregation of meiotic chromosomes, and the prevention of parthenogenetic activation. Central to many of these events appears to be the control by MAP kinase of cyclin translation and degradation.

Telomerase and immortalization

2019 ◽  
pp. 209-220
Author(s):  
Laura Collopy ◽  
Kazunori Tomita
Keyword(s):  
Cell Cycle ◽  
Growth And Development ◽  
Normal Cell ◽  
Chromosome Instability ◽  
Growth Arrest ◽  
Proliferative Capacity ◽  
Differentiated Cells ◽  
Dividing Cells ◽  
History Of ◽  
A Cell

The lifetime of a cell is set by the terminal ends of our chromosomes, ageing timers called telomeres. Most dividing cells, not exceptional for cancers, require telomeres to protect chromosomes. However, telomere erosion occurs at every cell cycle, thus imposing a proliferative capacity, eventually triggering a growth arrest. Cancer cells must overcome this proliferative limit in order to continue dividing. In the vast majority of cases, the growth and progression of cancers correlates with the upregulation of telomerase, an enzyme that replenishes telomeres. Telomerase is not active in normal, differentiated cells and its reactivation in cancer renders cells immortal and promotes their continued growth and development. Curiously, in cancer telomerase maintains short telomeres, retaining chromosome instability. Here, we briefly take you through history of cellular mortality with the connection to telomeres and telomerase and review their function in the normal cell to address their role during the transformation to malignancy.

scholarly journals TPR proteins required for anaphase progression mediate ubiquitination of mitotic B-type cyclins in yeast.

1996 ◽  
Vol 7 (5) ◽  
pp. 791-801 ◽  
Author(s):  
W Zachariae ◽  
K Nasmyth
Keyword(s):  
Cell Cycle ◽  
Cyclin B ◽  
Yeast Cells ◽  
Tetratricopeptide Repeat ◽  
Gene Products ◽  
Ubiquitin Pathway ◽  
Ubiquitin Protein Ligase ◽  
A Cell ◽  
Synthesis And Degradation

The abundance of B-type cyclin-CDK complexes is determined by regulated synthesis and degradation of cyclin subunits. Cyclin proteolysis is required for the final exit from mitosis and for the initiation of a new cell cycle. In extracts from frog or clam eggs, degradation is accompanied by ubiquitination of cyclin. Three genes, CDC16, CDC23, and CSE1 have recently been shown to be required specifically for cyclin B proteolysis in yeast. To test whether these genes are required for cyclin ubiquitination, we prepared extracts from G1-arrested yeast cells capable of conjugating ubiquitin to the B-type cyclin Clb2. The ubiquitination activity was cell cycle regulated, required Clb2's destruction box, and was low if not absent in cdc16, cdc23, cdc27, and cse1 mutants. Furthermore all these mutants were also defective in ubiquitination of another mitotic B-type cyclin, Clb3. The Cdc16, Cdc23, and Cdc27 proteins all contain several copies of the tetratricopeptide repeat and are subunits of a complex that is required for the onset of anaphase. The finding that gene products that are required for ubiquitination of Clb2 and Clb3 are also required for cyclin proteolysis in vivo provides the best evidence so far that cyclin B is degraded via the ubiquitin pathway in living cells. Xenopus homologues of Cdc16 and Cdc27 have meanwhile been shown to be associated with a 20S particle that appears to function as a cell cycle-regulated ubiquitin-protein ligase.

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 Neurogenic decisions require a cell cycle independent function of the CDC25B phosphatase

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Frédéric Bonnet ◽  
Angie Molina ◽  
Mélanie Roussat ◽  
Manon Azais ◽  
Sophie Bel-Vialar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Neural Progenitors ◽  
Apical Surface ◽  
Independent Function ◽  
M Cell ◽  
Stem Cell Maintenance ◽  
A Cell ◽  
Cell Cycle Dynamics ◽  
Cell Cycle Length

A fundamental issue in developmental biology and in organ homeostasis is understanding the molecular mechanisms governing the balance between stem cell maintenance and differentiation into a specific lineage. Accumulating data suggest that cell cycle dynamics play a major role in the regulation of this balance. Here we show that the G2/M cell cycle regulator CDC25B phosphatase is required in mammals to finely tune neuronal production in the neural tube. We show that in chick neural progenitors, CDC25B activity favors fast nuclei departure from the apical surface in early G1, stimulates neurogenic divisions and promotes neuronal differentiation. We design a mathematical model showing that within a limited period of time, cell cycle length modifications cannot account for changes in the ratio of the mode of division. Using a CDC25B point mutation that cannot interact with CDK, we show that part of CDC25B activity is independent of its action on the cell cycle.

scholarly journals Cell Cycle-dependent Regulation of Structure of Endoplasmic Reticulum and Inositol 1,4,5-Trisphosphate-induced Ca2+ Release in Mouse Oocytes and Embryos

2003 ◽  
Vol 14 (1) ◽  
pp. 288-301 ◽  
Author(s):  
Greg FitzHarris ◽  
Petros Marangos ◽  
John Carroll
Keyword(s):  
Cell Cycle ◽  
Endoplasmic Reticulum ◽  
Mitotic Spindle ◽  
Mitotic Division ◽  
Cyclin B ◽  
Dependent Manner ◽  
Inositol 1,4,5 Trisphosphate ◽  
A Cell ◽  
Cycle Dependent ◽  
Mouse Eggs

The organization of endoplasmic reticulum (ER) was examined in mouse eggs undergoing fertilization and in embryos during the first cell cycle. The ER in meiosis II (MII)-arrested mouse eggs is characterized by accumulations (clusters) that are restricted to the cortex of the vegetal hemisphere of the egg. Monitoring ER structure with DiI18 after egg activation has demonstrated that ER clusters disappear at the completion of meiosis II. The ER clusters can be maintained by inhibiting the decrease in cdk1-cyclin B activity by using the proteasome inhibitor MG132, or by microinjecting excess cyclin B. A role for cdk1-cyclin B in ER organization is further suggested by the finding that the cdk inhibitor roscovitine causes the loss of ER clusters in MII eggs. Cortical clusters are specific to meiosis as they do not return in the first mitotic division; rather, the ER aggregates around the mitotic spindle. Inositol 1,4,5-trisphosphate-induced Ca2+ release is also regulated in a cell cycle-dependent manner where it is increased in MII and in the first mitosis. The cell cycle dependent effects on ER structure and inositol 1,4,5-trisphosphate-induced Ca2+ release have implications for understanding meiotic and mitotic control of ER structure and inheritance, and of the mechanisms regulating mitotic Ca2+signaling.

scholarly journals Translational control of lipogenesis links protein synthesis and phosphoinositide signaling with nuclear division

2021 ◽  
Author(s):  
Nairita Maitra ◽  
Staci Hammer ◽  
Clara Kjerfve ◽  
Vytas A. Bankaitis ◽  
Michael Polymenis
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Fatty Acid Synthase ◽  
Nuclear Division ◽  
Phosphoinositide Signaling ◽  
Signaling Axis ◽  
Dividing Cells ◽  
A Cell ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol 4

ABSTRACTContinuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it. Here, we show that translational upregulation of lipogenic enzymes in yeast increased the abundance of lipids and accelerated nuclear elongation and division. De-repressing translation of acetyl CoA carboxylase and fatty acid synthase also suppressed cell cycle-related phenotypes, including delayed nuclear division, associated with Sec14p phosphatidylinositol transfer protein deficiencies, and the irregular nuclear morphologies of mutants defective in phosphatidylinositol 4-OH kinase activities. Our results show that increased lipogenesis drives a critical cell cycle landmark and report a phosphoinositide signaling axis in control of nuclear division. The broad conservation of these lipid metabolic and signaling pathways raises the possibility these activities similarly govern nuclear division in mammals.

Mutations of the fizzy locus cause metaphase arrest in Drosophila melanogaster embryos

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 359-376 ◽  
Author(s):  
I.A. Dawson ◽  
S. Roth ◽  
M. Akam ◽  
S. Artavanis-Tsakonas
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Drosophila Melanogaster ◽  
Double Mutant ◽  
Nuclear Division ◽  
Normal Function ◽  
Metaphase Arrest ◽  
Nervous Systems ◽  
Dividing Cells ◽  
A Cell

We describe the effects of mutations in the fizzy gene of Drosophila melanogaster and show that fizzy mutations cause cells in mitosis to arrest at metaphase. We show that maternally supplied fizzy activity is required for normal nuclear division in the preblastoderm embryo and, during later embryogenesis, that zygotic fizzy activity is required for the development of the ventrally derived epidermis and the central and peripheral nervous systems. In fizzy embryos, dividing cells in these tissues arrest at metaphase, fail to differentiate and ultimately die. In the ventral epidermis, if cells are prevented from entering mitosis by using a string mutation, cell death is prevented and the ability to differentiate ventral epidermis is restored in fizzy; string double mutant embryos. These results demonstrate that fizzy is a cell cycle mutation and that the normal function of the fizzy gene is required for dividing cells to exit metaphase and complete mitosis.

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