Cell-cycle-dependent telomere elongation by telomerase in budding yeast

2011 ◽  
Vol 31 (3) ◽  
pp. 169-177
Author(s):  
Shang Li
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Budding Yeast ◽  
Telomere Elongation ◽  
The Stability ◽  
Cycle Dependent ◽  
Linear Chromosomes ◽  
Telomere Chromatin

Telomeres are essential for the stability and complete replication of linear chromosomes. Telomere elongation by telomerase counteracts the telomere shortening due to the incomplete replication of chromosome ends by DNA polymerase. Telomere elongation is cell-cycle-regulated and coupled to DNA replication during S-phase. However, the molecular mechanisms that underlie such cell-cycle-dependent telomere elongation by telomerase remain largely unknown. Several aspects of telomere replication in budding yeast, including the modulation of telomere chromatin structure, telomere end processing, recruitment of telomere-binding proteins and telomerase complex to telomere as well as the coupling of DNA replication to telomere elongation during cell cycle progression will be discussed, and the potential roles of Cdk (cyclin-dependent kinase) in these processes will be illustrated.

scholarly journals Asymmetric division yields progeny cells with distinct modes of regulating cell cycle-dependent chromosome methylation

2019 ◽  
Vol 116 (31) ◽  
pp. 15661-15670 ◽  
Author(s):  
Xiaofeng Zhou ◽  
Jiarui Wang ◽  
Jonathan Herrmann ◽  
W. E. Moerner ◽  
Lucy Shapiro
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Single Molecule ◽  
Transcriptional Activation ◽  
Dna Methyltransferase ◽  
Cell Cycle Progression ◽  
Asymmetric Cell Division ◽  
Chromosomal Dna ◽  
C Terminus ◽  
Cycle Dependent

The cell cycle-regulated methylation state of Caulobacter DNA mediates the temporal control of transcriptional activation of several key regulatory proteins. Temporally controlled synthesis of the CcrM DNA methyltransferase and Lon-mediated proteolysis restrict CcrM to a specific time in the cell cycle, thereby allowing the maintenance of the hemimethylated state of the chromosome during the progression of DNA replication. We determined that a chromosomal DNA-based platform stimulates CcrM degradation by Lon and that the CcrM C terminus both binds to its DNA substrate and is recognized by the Lon protease. Upon asymmetric cell division, swarmer and stalked progeny cells employ distinct mechanisms to control active CcrM. In progeny swarmer cells, CcrM is completely degraded by Lon before its differentiation into a replication-competent stalked cell later in the cell cycle. In progeny stalked cells, however, accumulated CcrM that has not been degraded before the immediate initiation of DNA replication is sequestered to the cell pole. Single-molecule imaging demonstrated physical anticorrelation between sequestered CcrM and chromosomal DNA, thus preventing DNA remethylation. The distinct control of available CcrM in progeny swarmer and stalked cells serves to protect the hemimethylated state of DNA during chromosome replication, enabling robustness of cell cycle progression.

scholarly journals Deacetylation of catalytic lysine in CDK1 is essential for Cyclin-B binding and cell cycle

2018 ◽  
Author(s):  
Shaunak Deota ◽  
Sivasudhan Rathnachalam ◽  
Kanojia Namrata ◽  
Mayank Boob ◽  
Amit Fulzele ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Resolution ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Current Model ◽  
Cyclin B ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Evolutionarily Conserved ◽  
Cycle Dependent

AbstractCyclin-dependent-kinases (CDKs) are essential for cell cycle progression. While dependence of CDK activity on Cyclin levels is established, molecular mechanisms that regulate their binding are less studied. Here, we show that CDKl:Cyclin-B interactions are regulated by acetylation, which was hitherto unknown. We demonstrate that cell cycle dependent acetylation of the evolutionarily conserved catalytic lysine in CDK1 or eliminating its charge state abrogates Cyclin-B binding. Opposing activities of SIRT1 and P300 regulate acetylation, which marks a reserved pool of CDK1. Our high resolution structural analyses into the formation of kinase competent CDK1: Cyclin-B complex have unveiled long-range effects of catalytic lysine in configuring the CDK1 interface for Cyclin-B binding. Cells expressing acetylation mimic mutant of Cdc2 in yeast are arrested in G2 and fail to divide. Thus, by illustrating cell cycle dependent deacetylation as a determinant of CDK1:Cyclin-B interaction, our results redefine the current model of CDK1 activation and cell cycle progression.

Fission yeast Nda1 and Nda4, MCM homologs required for DNA replication, are constitutive nuclear proteins

1996 ◽  
Vol 109 (2) ◽  
pp. 319-326 ◽  
Author(s):  
N. Okishio ◽  
Y. Adachi ◽  
M. Yanagida
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Fission Yeast ◽  
Budding Yeast ◽  
Affinity Column ◽  
Wild Type ◽  
M Phase ◽  
A Cell ◽  
Mcm Proteins ◽  
Cycle Dependent

The nda1+ and nda4+ genes of the fission yeast Schizosaccharomyces pombe encode proteins similar to budding yeast MCM2 and MCM5/CDC46, respectively, which are required for the early stages of DNA replication. The budding yeast Mcm proteins display cell-cycle dependent localization. They are present in the nucleus specifically from late M phase until the beginning of S phase, so that they were suggested to be components of a replication licensing factor, a positive factor for the onset of replication, which is thought to be inactivated after use, thus restricting replication to only once in a cell cycle. In the present study, we raised antibodies against Nda1 or Nda4 and identified 115 kDa and 80 kDa proteins, respectively. Their immunolocalization was examined in wild-type cells and in various cell-cycle mutants. Both Nda1 and Nda4 proteins remained primarily in the nucleus throughout the cell cycle. In mutants arrested in G1, S, and G2 phases, these proteins were also enriched in the nucleus. These results indicate that the dramatic change in subcellular localization as seen in budding yeast is not essential in fission yeast for the functions of Nda1 and Nda4 proteins to be executed. The histidine-tagged nda1+ gene was constructed and integrated into the chromosome to replace the wild-type nda1+ gene. The resulting His-tagged Nda1 protein was adsorbed to the Ni-affinity column, and co-eluted with the untagged Nda4 protein, suggesting that they formed a complex.

scholarly journals RUNX3 regulates cell cycle-dependent chromatin dynamics by functioning as a pioneer factor of the restriction point

2018 ◽  
Author(s):  
Jung-Won Lee ◽  
Da-Mi Kim ◽  
Ju-Won Jang ◽  
Tae-Geun Park ◽  
You-Soub Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Biology ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cell Cycle Regulators ◽  
Restriction Point ◽  
Trithorax Group ◽  
Chromatin Dynamics ◽  
Pioneer Factor ◽  
Cycle Dependent

AbstractThe cellular decision regarding whether to undergo proliferation or death is made at the restriction (R)-point, which is disrupted in nearly all tumors. The identity of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in cell biology. We found that early after mitogenic stimulation, RUNX3 bound to its target loci, where it opened chromatin structure by sequential recruitment of Trithorax group proteins and cell-cycle regulators to drive cells to the R-point. Soon after, RUNX3 closed these loci by recruiting Polycomb repressor complexes, causing the cell to pass through the R-point toward S phase. If the RAS signal was constitutively activated, RUNX3 inhibited cell cycle progression by maintaining R-point-associated genes in an open structure. Our results identify RUNX3 as a pioneer factor for the R-point and reveal the molecular mechanisms by which appropriate chromatin modifiers are selectively recruited to target loci for appropriate R-point decisions.

scholarly journals PAR-4/LKB1 regulates DNA replication during asynchronous division of the early C. elegans embryo

2014 ◽  
Vol 205 (4) ◽  
pp. 447-455 ◽  
Author(s):  
Laura Benkemoun ◽  
Catherine Descoteaux ◽  
Nicolas T. Chartier ◽  
Lionel Pintard ◽  
Jean-Claude Labbé
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Cycle Duration ◽  
Cell Stage ◽  
C Elegans ◽  
Stage Embryo ◽  
Regulation Of Cell Cycle

Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division.

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals Budding yeast relies on G1 cyclin specificity to couple cell cycle progression with morphogenetic development

2021 ◽  
Vol 7 (23) ◽  
pp. eabg0007
Author(s):  
Deniz Pirincci Ercan ◽  
Florine Chrétien ◽  
Probir Chakravarty ◽  
Helen R. Flynn ◽  
Ambrosius P. Snijders ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Quantitative Model ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Model Cell ◽  
Mitotic Cyclin ◽  
Substrate Phosphorylation ◽  
The Cost

Two models have been put forward for cyclin-dependent kinase (Cdk) control of the cell cycle. In the qualitative model, cell cycle events are ordered by distinct substrate specificities of successive cyclin waves. Alternatively, in the quantitative model, the gradual rise of Cdk activity from G1 phase to mitosis leads to ordered substrate phosphorylation at sequential thresholds. Here, we study the relative contributions of qualitative and quantitative Cdk control in Saccharomyces cerevisiae. All S phase and mitotic cyclins can be replaced by a single mitotic cyclin, albeit at the cost of reduced fitness. A single cyclin can also replace all G1 cyclins to support ordered cell cycle progression, fulfilling key predictions of the quantitative model. However, single-cyclin cells fail to polarize or grow buds and thus cannot survive. Our results suggest that budding yeast has become dependent on G1 cyclin specificity to couple cell cycle progression to essential morphogenetic events.

Exogenous ATP induces a limited cell cycle progression of arterial smooth muscle cells

1993 ◽  
Vol 264 (4) ◽  
pp. C783-C788 ◽  
Author(s):  
R. Malam-Souley ◽  
M. Campan ◽  
A. P. Gadeau ◽  
C. Desgranges
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cell Cycle Progression ◽  
Mrna Level ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Cycle Progression ◽  
Arterial Smooth Muscle Cells ◽  
Cycle Dependent

Because exogenous ATP is suspected to influence the proliferative process, its effects on the cell cycle progression of arterial smooth muscle cells were studied by investigating changes in the mRNA steady-state level of cell cycle-dependent genes. Stimulation of cultured quiescent smooth muscle cells by exogenous ATP induced chronological activation not only of immediate-early but also of delayed-early cell cycle-dependent genes, which were usually expressed after a mitogenic stimulation. In contrast, ATP did not increase late G1 gene mRNA level, demonstrating that this nucleotide induces a limited cell cycle progression of arterial smooth muscle cells through the G1 phase but is not able by itself to induce crossing over the G1-S boundary and consequently DNA synthesis. An increase in c-fos mRNA level was also induced by ADP but not by AMP or adenosine. Moreover, 2-methylthioadenosine 5'-triphosphate but not alpha, beta-methyleneadenosine 5'-triphosphate mediated this kind of response. Taken together, these results demonstrate that extracellular ATP induces the limited progression of arterial smooth muscle cells through the G1 phase via its fixation on P2 gamma receptors.

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