Search results for "cycle"

Asymmetric cell division requires specific mechanisms for adjusting global transcription

2017

Most cells divide symmetrically into two approximately identical cells. There are many examples, however, of asymmetric cell division that can generate sibling cell size differences. Whereas physical asymmetric division mechanisms and cell fate consequences have been investigated, the specific problem caused by asymmetric division at the transcription level has not yet been addressed. In symmetrically dividing cells the nascent transcription rate increases in parallel to cell volume to compensate it by keeping the actualmRNA synthesis rate constant. This cannot apply to the yeast Saccharomyces cerevisiae, where this mechanism would provoke a neverending increasing mRNA synthesis rate in sma…

Whi7 is an unstable cell-cycle repressor of the Start transcriptional program

2017

Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program by G1 CDK-cyclin complexes through the inactivation of Start transcriptional repressors, Whi5 in yeast or Rb in mammals. Here we provide novel keys of how Whi7, a protein related at sequence level to Whi5, represses Start. Whi7 is an unstable protein, degraded by the SCFGrr1 ubiquitin-ligase, whose stability is cell cycle regulated by CDK1 phosphorylation. Importantly, Whi7 associates to G1/S gene promoters in late G1 acting as a repressor of SBF-dependent transcription. Our results demonstrate that Whi7 is a ge…

A comparative study of the degradation of yeast cyclins Cln1 and Cln2.

2016

The yeast cyclins Cln1 and Cln2 are very similar in both sequence and function, but some differences in their functionality and localization have been recently described. The control of Cln1 and Cln2 cellular levels is crucial for proper cell cycle initiation. In this work, we analyzed the degradation patterns of Cln1 and Cln2 in order to further investigate the possible differences between them. Both cyclins show the same half‐life but, while Cln2 degradation depends on ubiquitin ligases SCFG rr1 and SCFC dc4, Cln1 is affected only by SCFG rr1. Degradation analysis of chimeric cyclins, constructed by combining fragments from Cln1 and Cln2, identifies the N‐terminal sequence of the proteins…

2021

Despite recent advancements in tumor therapy, metastasis and tumor relapse remain major complications hindering the complete recovery of many cancer patients. Dormant tumor cells, which reside in the body, possess the ability to re-enter the cell cycle after therapy. This phenomenon has been attributed to therapy-induced senescence. We show that these cells could be targeted by the use of zinc oxide nanoparticles (ZnO NPs). In the present study, the properties of tumor cells after survival of 16 Gy gamma-irradiation were investigated in detail. Analysis of morphological features, proliferation, cell cycle distribution, and protein expression revealed classical hallmarks of senescent cells a…

Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle

2017

Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively. Consequently, the coordination of TERRA degradation with telomere r…

Sustained oscillations in the MAP kinase cascade.

2016

Abstract The MAP kinase cascade is a network of enzymatic reactions arranged in layers. In each layer occurs a multiple futile cycle of phosphorylations. The fully phosphorylated substrate then serves as an enzyme for the layer below. This paper focuses on the existence of parameters for which Hopf bifurcations occur and generate periodic orbits. Furthermore it is explained how geometric singular perturbation theory allows to generalize results from simple models to more complex ones.

Characterization of Hydrothermal Processing Influence on Strontium Substituted Apatite by Investigating Stable Oxygen Isotope Ratio and Antibacterial…

2018

Synthetic hydroxyapatite (HAp) has weak antibacterial and mechanical properties. The antibacterial activity of HAp can be enhanced by strontium cation substitution and incorporation of peroxide ion via hydrothermal processing at 100 °C and 150 °C temperature using 50% H2O2 solution. The starting reagents and products of HAp processing were analyzed by thermal conversion elemental analyser – isotopic ratio mass spectrometer in order to determine the δ18O values. Using different host materials it could be possible to determine differences of δ18O values between untreated and hydrothermally treated HAp samples. The enhanced antibacterial properties of processed HAp samples were investigated us…

Cytotoxicity of seven naturally occurring phenolic compounds towards multi-factorial drug-resistant cancer cells

2016

Abstract Introduction In medical oncology, multi-drug resistance (MDR) of cancer cells continues to be a major impediment. We are in quest of novel anti-proliferative agents to overcome drug-resistant tumor cells. Methods In the present study, we investigated the cytotoxicity of 7 naturally occurring phenolic compounds including two isoflavonoids alpinumisoflavone ( 1 ) and laburnetin ( 2 ), one biflavonoid amentoflavone ( 3) , three lignans pycnanthulignene A ( 4 ), pycnanthulignene B ( 5 ), and syringaresinol ( 7 ) and one xanthone, euxanthone ( 6 ) against 9 drug-sensitive and MDR cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, w…

One-Cell Doubling Evaluation by Living Arrays of Yeast, ODELAY!

2016

Abstract Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single-cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony formin…

Characterizing diversity in the tumor-immune microenvironment of distinct subclasses of gastroesophageal adenocarcinomas

2020

Background Gastroesophageal adenocarcinomas (GEAs) are heterogeneous cancers where immune checkpoint inhibitors have robust efficacy in heavily inflamed microsatellite instability (MSI) or Epstein-Barr virus (EBV)-positive subtypes. Immune checkpoint inhibitor responses are markedly lower in diffuse/genome stable (GS) and chromosomal instable (CIN) GEAs. In contrast to EBV and MSI subtypes, the tumor microenvironment of CIN and GS GEAs have not been fully characterized to date, which limits our ability to improve immunotherapeutic strategies. Patients and methods Here we aimed to identify tumor-immune cell association across GEA subclasses using data from The Cancer Genome Atlas (N = 453 GE…