scholarly journals Novel localization and possible functions of cyclin E in early sea urchin development

2002 ◽  
Vol 115 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Bradley J. Schnackenberg ◽  
William F. Marzluff
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Sea Urchin ◽  
Kinase Activity ◽  
Cyclin E ◽  
Sperm Head ◽  
Mitotic Spindles ◽  
Paternal Genome ◽  
Cell Cycles ◽  
Cdk2 Activity

In somatic cells, cyclin E-cdk2 activity oscillates during the cell cycle and is required for the regulation of the G1/S transition. Cyclin E and its associated kinase activity remain constant throughout early sea urchin embryogenesis, consistent with reports from studies using several other embryonic systems. Here we have expanded these studies and show that cyclin E rapidly and selectively enters the sperm head after fertilization and remains concentrated in the male pronucleus until pronuclear fusion, at which time it disperses throughout the zygotic nucleus. We also show that cyclin E is not concentrated at the centrosomes but is associated with condensed chromosomes throughout mitosis for at least the first four cell cycles. Isolated mitotic spindles are enriched for cyclin E and cdk2, which are localized to the chromosomes. The chromosomal cyclin E is associated with active kinase during mitosis. We propose that cyclin E may play a role in the remodeling of the sperm head and re-licensing of the paternal genome after fertilization. Furthermore, cyclin E does not need to be degraded or dissociated from the chromosomes during mitosis; instead, it may be required on chromosomes during mitosis to immediately initiate the next round of DNA replication.

scholarly journals MAD1 and p27KIP1 Cooperate To Promote Terminal Differentiation of Granulocytes and To Inhibit Myc Expression and Cyclin E-CDK2 Activity

2002 ◽  
Vol 22 (9) ◽  
pp. 3014-3023 ◽  
Author(s):  
Grant A. McArthur ◽  
Kevin P. Foley ◽  
Matthew L. Fero ◽  
Carl R. Walkley ◽  
Andrew J. Deans ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Cyclin E ◽  
Null Alleles ◽  
Cyclin Dependent Kinase ◽  
Similar Treatment ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cdk2 Activity ◽  
Differentiation Inducer

ABSTRACT To understand how cellular differentiation is coupled to withdrawal from the cell cycle, we have focused on two negative regulators of the cell cycle, the MYC antagonist MAD1 and the cyclin-dependent kinase inhibitor p27KIP1. Generation of Mad1/p27KIP1 double-null mice revealed a number of synthetic effects between the null alleles of Mad1 and p27KIP1, including embryonic lethality, increased proliferation, and impaired differentiation of granulocyte precursors. Furthermore, with granulocyte cell lines derived from the Mad1/p27KIP1 double-null mice, we observed constitutive Myc expression and cyclin E-CDK2 kinase activity as well as impaired differentiation following treatment with an inducer of differentiation. By contrast, similar treatment of granulocytes from Mad1 or p27KIP1 single-null mice resulted in differentiation accompanied by downregulation of both Myc expression and cyclin E-CDK2 kinase activity. In the double-null granulocytic cells, addition of a CDK2 inhibitor in the presence of differentiation inducer was sufficient to restore differentiation and reduce Myc levels. We conclude that Mad1 and p27KIP1 operate, at least in part, by distinct mechanisms to downregulate CDK2 activity and Myc expression in order to promote cell cycle exit during differentiation.

Wachstumsparameter in normalen und durch Actinomycin verlängerten Zellzyklen von Tetrahymena / Growth Parameters in Normal and Actinomycin-induced prolonged Cell Cycles of Tetrahymena

1969 ◽  
Vol 24 (12) ◽  
pp. 1624-1629 ◽  
Author(s):  
Günter Cleffmann
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Growth ◽  
Rna Synthesis ◽  
Growth Parameters ◽  
Average Duration ◽  
Cell Cycles ◽  
Growing Cell

Actinomycin in low concentration (0,2 μg/ml — 0,5 μg/ml) prolongs the average duration of the cell cycle of Tetrahymena considerably, but does not inhibit cell division completely. Some parameters of the growing cell have been tested in cell cycles extended in this way and compared to those of normally growing cells. The RNA synthesis of treated cells is reduced to such an extent that the RNA content per cell decreases during the prolonged cell cycle. Nevertheless cell growth, protein synthesis and DNA replication proceed at almost the same rate as in untreated cells. These findings indicate that the presence of actinomycin does not interfere with RNA fractions necessary for growth but reduce the synthesis of RNA fractions which are essential for cell division. Therefore a longer period is needed for their accumulation.

scholarly journals A Role for Cdk2 Kinase in Negatively Regulating DNA Replication during S Phase of the Cell Cycle

1997 ◽  
Vol 137 (1) ◽  
pp. 183-192 ◽  
Author(s):  
Xuequn Helen Hua ◽  
Hong Yan ◽  
John Newport
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cyclin E ◽  
Embryonic Cell ◽  
S Phase ◽  
Negative Regulation ◽  
Sperm Chromatin ◽  
High Concentration ◽  
Low Concentrations ◽  
Embryonic Cell Cycle

Using cell-free extracts made from Xenopus eggs, we show that cdk2-cyclin E and A kinases play an important role in negatively regulating DNA replication. Specifically, we demonstrate that the cdk2 kinase concentration surrounding chromatin in extracts increases 200-fold once the chromatin is assembled into nuclei. Further, we find that if the cdk2–cyclin E or A concentration in egg cytosol is increased 16-fold before the addition of sperm chromatin, the chromatin fails to initiate DNA replication once assembled into nuclei. This demonstrates that cdk2–cyclin E or A can negatively regulate DNA replication. With respect to how this negative regulation occurs, we show that high levels of cdk2–cyclin E do not block the association of the protein complex ORC with sperm chromatin but do prevent association of MCM3, a protein essential for replication. Importantly, we find that MCM3 that is prebound to chromatin does not dissociate when cdk2– cyclin E levels are increased. Taken together our results strongly suggest that during the embryonic cell cycle, the low concentrations of cdk2–cyclin E present in the cytosol after mitosis and before nuclear formation allow proteins essential for potentiating DNA replication to bind to chromatin, and that the high concentration of cdk2–cyclin E within nuclei prevents MCM from reassociating with chromatin after replication. This situation could serve, in part, to limit DNA replication to a single round per cell cycle.

scholarly journals MAP kinase dependent cyclinE/cdk2 activity promotes DNA replication in early sea urchin embryos

2009 ◽  
Vol 334 (2) ◽  
pp. 383-394 ◽  
Author(s):  
J. Kisielewska ◽  
R. Philipova ◽  
J.-Y. Huang ◽  
M. Whitaker
Keyword(s):  
Dna Replication ◽  
Map Kinase ◽  
Sea Urchin ◽  
Sea Urchin Embryos ◽  
Cdk2 Activity

scholarly journals Chromosome Association of Minichromosome Maintenance Proteins in Drosophila Mitotic Cycles

1997 ◽  
Vol 139 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Tin Tin Su ◽  
Patrick H. O'Farrell
Keyword(s):  
Cell Cycle ◽  
Cyclin E ◽  
Embryonic Cell ◽  
Cyclin B ◽  
Chromatin Interaction ◽  
G1 Phase ◽  
Minichromosome Maintenance ◽  
Cell Cycles ◽  
Mcm Proteins ◽  
Replication Factors

Minichromosome maintenance (MCM) proteins are essential DNA replication factors conserved among eukaryotes. MCMs cycle between chromatin bound and dissociated states during each cell cycle. Their absence on chromatin is thought to contribute to the inability of a G2 nucleus to replicate DNA. Passage through mitosis restores the ability of MCMs to bind chromatin and the ability to replicate DNA. In Drosophila early embryonic cell cycles, which lack a G1 phase, MCMs reassociate with condensed chromosomes toward the end of mitosis. To explore the coupling between mitosis and MCM–chromatin interaction, we tested whether this reassociation requires mitotic degradation of cyclins. Arrest of mitosis by induced expression of nondegradable forms of cyclins A and/or B showed that reassociation of MCMs to chromatin requires cyclin A destruction but not cyclin B destruction. In contrast to the earlier mitoses, mitosis 16 (M16) is followed by G1, and MCMs do not reassociate with chromatin at the end of M16. dacapo mutant embryos lack an inhibitor of cyclin E, do not enter G1 quiescence after M16, and show mitotic reassociation of MCM proteins. We propose that cyclin E, inhibited by Dacapo in M16, promotes chromosome binding of MCMs. We suggest that cyclins have both positive and negative roles in controlling MCM–chromatin association.

Inhibition by aphidicolin of cell cycle progression and DNA replication in sea urchin embryos

1979 ◽  
Vol 100 (3) ◽  
pp. 439-444 ◽  
Author(s):  
Susumu Ikegami ◽  
Shonan Amemiya ◽  
Mieko Oguro ◽  
Hiroshi Nagano ◽  
Yoshitake Mano
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Sea Urchin ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Sea Urchin Embryos

scholarly journals Evidence for polarity of chromosome replication in F−strains ofEscherichia coli

1966 ◽  
Vol 8 (1) ◽  
pp. 119-124 ◽  
Author(s):  
W. D. Donachie ◽  
Millicent Masters
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
Dna Replication ◽  
Cell Separation ◽  
Chromosome Replication ◽  
Ofescherichia Coli ◽  
Cell Cycles ◽  
Gene Replication ◽  
Serine Deaminase

The inducibility of three enzymes (β-galactosidase, tryptophanase and D-serine deaminase) has been measured at various times during the cell cycles of three strains ofEscherichia coli(K12 58–161 F−, B/r F–and 15T−). In each strain sharp increases in inducibility of these enzymes occurred at characteristic periods in each cell cycle. Such increases depend on DNA replication and therefore probably reflect synchronized gene replication. It is inferred that chromosome replication in these F−strains is sequential from a fixed origin.Infection with F′Lack+results in an extra period of increase in inducibiity of β-galactosidase in each cell cycle. It is concluded that the F′ episome replicates once in each cell cycle at a time soon after cell separation.

scholarly journals Adenovirus E1B55K Region Is Required To Enhance Cyclin E Expression for Efficient Viral DNA Replication

2008 ◽  
Vol 82 (7) ◽  
pp. 3415-3427 ◽  
Author(s):  
Xinyu Zheng ◽  
Xiao-Mei Rao ◽  
Jorge G. Gomez-Gutierrez ◽  
Hongying Hao ◽  
Kelly M. McMasters ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Cells ◽  
Cyclin E ◽  
Serum Starvation ◽  
Viral Dna ◽  
Human Lung Fibroblast ◽  
Viral Dna Replication ◽  
Efficient Replication ◽  
Interfering Rna

ABSTRACT Adenoviruses (Ads) with E1B55K mutations can selectively replicate in and destroy cancer cells. However, the mechanism of Ad-selective replication in tumor cells is not well characterized. We have shown previously that expression of several cell cycle-regulating genes is markedly affected by the Ad E1b gene in WI-38 human lung fibroblast cells (X. Rao, et al., Virology 350:418-428, 2006). In the current study, we show that the Ad E1B55K region is required to enhance cyclin E expression and that the failure to induce cyclin E overexpression due to E1B55K mutations prevents viral DNA from undergoing efficient replication in WI-38 cells, especially when the cells are arrested in the G0 phase of the cell cycle by serum starvation. In contrast, cyclin E induction is less dependent on the function encoded in the E1B55K region in A549 and other cancer cells that are permissive for replication of E1B55K-mutated viruses, whether the cells are in the S phase or G0 phase. The small interfering RNA that specifically inhibits cyclin E expression partially decreased viral replication. Our study provides evidence suggesting that E1B55K may be involved in cell cycle regulation that is important for efficient viral DNA replication and that cyclin E overexpression in cancer cells may be associated with the oncolytic replication of E1B55K-mutated viruses.

scholarly journals Cdk2 Activity Is Dispensable for the Onset of DNA Replication during the First Mitotic Cycles of the Sea Urchin Early Embryo

1998 ◽  
Vol 200 (2) ◽  
pp. 182-197 ◽  
Author(s):  
Jean-Luc Moreau ◽  
François Marques ◽  
Abdelhamid Barakat ◽  
Philippe Schatt ◽  
Jean-Claude Lozano ◽  
...  
Keyword(s):  
Dna Replication ◽  
Sea Urchin ◽  
Early Embryo ◽  
Cdk2 Activity

scholarly journals CDK2 activity determines the timing of cell-cycle commitment and sequential DNA replication

2020 ◽  
Author(s):  
Sungsoo Kim ◽  
Alessandra Leong ◽  
Chellam Nayar ◽  
Minah Kim ◽  
Hee Won Yang
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Threshold Level ◽  
Cyclin Dependent Kinases ◽  
Safety Mechanism ◽  
Cdk2 Activity ◽  
Tightly Coupled ◽  
Rb Phosphorylation

AbstractTo enter the cell cycle, mammalian cells must cross a point of no return (the commitment point), after which they proceed through the cell cycle regardless of changes in external signaling. This process is tightly regulated by the cyclin-dependent kinases (CDKs) and downstream molecules such as retinoblastoma (Rb). Here we show that CDK2 activity coordinates the timing of cell-cycle commitment and DNA replication. CDK4/6 activation initiates Rb phosphorylation and E2F activity, causing a gradual increase in CDK2 activity. Once CDK2 activity reaches a threshold level, CDK2 triggers the commitment point by maintaining Rb phosphorylation and subsequently initiates DNA replication. While the timing of the commitment point is tightly coupled with DNA replication, our experiments, which acutely increased CDK2 activity, suggest that the timing of the commitment point is before DNA replication. These findings highlight how cells utilize a safety mechanism to maintain genome stability by protecting against incomplete DNA replication.

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