Cilastatin Modulates DPEP1- and IQGAP1-Associated Neuro-Glio-Vascular Inflammation in Oxaliplatin-Induced Peripheral Neurotoxicity.

Oxaliplatin-induced peripheral neurotoxicity (OIPN) represents a major challenge in cancer therapy, characterized by dorsal root ganglia (DRG) inflammation and disruption of neuro-glio-vascular unit function. In this study, we investigated the involvement of the scaffold protein IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) and dehydropeptidase-1 (DPEP1) in the DRG response to oxaliplatin (OxPt) and the modulatory effect of cilastatin. Behavioral assessment showed a robust nocifensive response to cold stimuli in OxPt-treated rats, attenuated by cilastatin co-treatment.

Continuous nuclear envelope surveillance is required for DNA double strand break repair.

Precise double-strand break (DSB) repair is paramount for genome stability. Homologous recombination (HR) is preferred to repair DSBs when a nearby sister chromatid ensures an error-free template. In Saccharomyces cerevisiae, this preference extends into anaphase and telophase (late mitosis; late-M) despite sister chromatids having been pulled apart.

Chromosome Segregation in Closed Mitosis Under an Excess of Nuclear Envelope.

Background: Two major types of cell division occur in eukaryotic cells regarding the dismantlement or not of the nuclear envelope (NE) in mitosis, open and closed mitosis, respectively. In the budding yeast Saccharomyces cerevisiae, the prototypical model for closed mitosis, the Nem1-Spo7 phosphatase complex, which regulates lipid metabolism, plays a key role in coordinating NE expansion throughout the cell cycle. Indeed, Nem1 depletion leads to abnormal NE evaginations in interphase, which protrude the ribosomal DNA (rDNA) and the nucleolus.

Dorsal root ganglion inflammation by oxaliplatin toxicity: DPEP1 as possible target for peripheral neuropathy prevention.

Background: Peripheral neuropathy (PN) constitutes a dose-limiting side effect of oxaliplatin chemotherapy that often compromises the efficacy of antineoplastic treatments. Sensory neurons damage in dorsal root ganglia (DRG) are the cellular substrate of PN complex molecular origin. Dehydropeptidase-1 (DPEP1) inhibitors have shown to avoid platin-induced nephrotoxicity without compromising its anticancer efficiency.

Exploring the Anticancer Potential of Phenolic -Triterpenes from Celastraceae Species.

To explore new compounds with antitumour activity, fifteen phenolic -tripterpenes isolated from Celastraceae species, , and , have been studied. Their chemical structures were elucidated through spectroscopic and spectrometric techniques, resulting in the identification of three novel chemical compounds. Evaluation on human tumour cell lines (A549 and SW1573, non-small cell lung; HBL-100 and T-47D, breast; HeLa, cervix, and WiDr, colon) revealed that three compounds, named 6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral, exhibited significant activity (GI ranging from 0.

Msc1 is a nuclear envelope protein that reinforces DNA repair in late mitosis.

Precise double-strand break (DSB) repair is a paramount for genome stability. Homologous recombination (HR) repairs DSBs when cyclin-dependent kinase (CDK) activity is high, which correlates with the availability of the sister chromatid as a template. However, anaphase and telophase are paradoxical scenarios since high CDK favors HR despite sister chromatids being no longer aligned.

The CRISPR/Cas9 system forms a condensate in the yeast nucleus.

CRISPR/Cas9 gene editing technology has revolutionized genetic engineering. However, the nuclear dynamics of Cas9 in eukaryotic cells, particularly in the model organism , remains poorly understood. Here, we constructed yeast strains expressing fluorescently tagged Cas9 variants, revealing their accumulation in the nucleus over time.

Effect of carrier yeast RNAs in the detection of SARS-CoV-2 by RT-LAMP.

The COVID-19 pandemic caused by SARS-CoV-2 has underscored the need for rapid and accurate diagnostic methods. Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) has emerged as a promising molecular tool in least developed countries due to its simplicity, speed, and sensitivity. Nevertheless, reliable SARS-CoV-2 detection can be challenged by the chain custody of the samples.

A Yeast Mitotic Tale for the Nucleus and the Vacuoles to Embrace.

The morphology of the nucleus is roughly spherical in most eukaryotic cells. However, this organelle shape needs to change as the cell travels through narrow intercellular spaces during cell migration and during cell division in organisms that undergo closed mitosis, i.e.

A simplified and easy-to-use HIP HOP assay provides insights into chalcone antifungal mechanisms of action.

Elucidating the mechanism of action of an antifungal or cytotoxic compound is a time-consuming process. Yeast chemogenomic profiling provides a compelling solution to the problem but is experimentally complex. Here, we demonstrate the use of a highly simplified yeast chemical genetic assay comprising just 89 yeast deletion strains, each diagnostic for a specific mechanism of action.

The vacuole shapes the nucleus and the ribosomal DNA loop during mitotic delays.

The ribosomal DNA (rDNA) array of has served as a model to address chromosome organization. In cells arrested before anaphase (mid-M), the rDNA acquires a highly structured chromosomal organization referred to as the rDNA loop, whose length can double the cell diameter. Previous works established that complexes such as condensin and cohesin are essential to attain this structure.

Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes.

The key role of Topoisomerase II (Top2) is the removal of topological intertwines between sister chromatids. In yeast, inactivation of Top2 brings about distinct cell cycle responses. In the case of the conditional top2-5 allele, interphase and mitosis progress on schedule but cells suffer from a chromosome segregation catastrophe.

Implications of Metastable Nicks and Nicked Holliday Junctions in Processing Joint Molecules in Mitosis and Meiosis.

Joint molecules (JMs) are intermediates of homologous recombination (HR). JMs rejoin sister or homolog chromosomes and must be removed timely to allow segregation in anaphase. Current models pinpoint Holliday junctions (HJs) as a central JM.

Are Anaphase Events Really Irreversible? The Endmost Stages of Cell Division and the Paradox of the DNA Double-Strand Break Repair.

It has been recently demonstrated that yeast cells are able to partially regress chromosome segregation in telophase as a response to DNA double-strand breaks (DSBs), likely to find a donor sequence for homology-directed repair (HDR). This regression challenges the traditional concept that establishes anaphase events as irreversible, hence opening a new field of research in cell biology. Here, the nature of this new behavior in yeast is summarized and the underlying mechanisms are speculated about.

Yeast cells can partially revert chromosome segregation to repair late DNA double-strand breaks through homologous recombination.

DNA repair in late mitosis sets paradoxical scenarios. Cyclin-dependent kinase (CDK) activity is high, which favors homologous recombination (HR), despite a sister chromatid is not physically close to recombine with. We have found that DNA double-strand breaks partially revert chromosome segregation to find an intact template and repair through HR.

Publisher Correction: DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer.

Once thought a mere ribosome factory, the nucleolus has been viewed in recent years as an extremely sensitive gauge of diverse cellular stresses. Emerging concepts in nucleolar biology include the nucleolar stress response (NSR), whereby a series of cell insults have a special impact on the nucleolus. These insults include, among others, ultra-violet radiation (UV), nutrient deprivation, hypoxia and thermal stress.

DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci.

DNA double strand breaks (DSBs) pose a high risk for genome integrity. Cells repair DSBs through homologous recombination (HR) when a sister chromatid is available. HR is upregulated by the cycling dependent kinase (CDK) despite the paradox of telophase, where CDK is high but a sister chromatid is not nearby.

Fanconi Anaemia-Like Mph1 Helicase Backs up Rad54 and Rad5 to Circumvent Replication Stress-Driven Chromosome Bridges.

Homologous recombination (HR) is a preferred mechanism to deal with DNA replication impairments. However, HR synapsis gives rise to joint molecules (JMs) between the nascent sister chromatids, challenging chromosome segregation in anaphase. Joint molecules are resolved by the actions of several structure-selective endonucleases (SSEs), helicases and topoisomerases.