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PRDX1 Counteracts Catastrophic Telomeric Cleavage Events That Are Triggered by DNA Repair Activities Post Oxidative Damage

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Deconvolution of ex-vivo drug screening data and bulk tissue expression predicts the abundance and viability of cancer cell subpopulations

Alexandre Coudray

Ex-vivo drug sensitivity screening (DSS) allows the prediction of cancer treatment effectiveness in a personalized fashion. However, it only provides a readout on mixtures of cells, potentially occulting important information on clinically relevant cell su ...

EPFL2023

2D MoS2 Nanopores: Wafer-scale Fabrication and Monolayer Stability for Long-term Single-Molecule Sensing

Mukeshchand Thakur

Biologically inspired solid-state nanopores are artificial openings or apertures in thin membranes similar to natural protein ion channels in a lipid bilayer of cell membranes. In solid-state nanopores, a thin insulating membrane with single or multiple po ...

EPFL2022

Cellularization across eukaryotes: Conserved mechanisms and novel strategies

Omaya Pierre Dudin

Many eukaryotes form multinucleated cells during their devel-opment. Some cells persist as such during their lifetime, others choose to cleave each nucleus individually using a specialized cytokinetic process known as cellularization. What is cellula-rizat ...

CURRENT BIOLOGY LTD2023

Identifying the mediators of intracellular E. coli inactivation under UVA light: The (photo) Fenton process and singlet oxygen

César Pulgarin, Stefanos Giannakis

Solar disinfection (SODIS) was probed for its underlying mechanism. When Escherichia coli was exposed to UVA irradiation, the dominant solar fraction acting in SODIS process, cells exhibited a shoulder before death ensued. This profile resembles cell killi ...

PERGAMON-ELSEVIER SCIENCE LTD2022

Allosteric control of type I-A CRISPR-Cas3 complexes and establishment as effective nucleic acid detection and human genome editing tools

Henning Paul-Julius Stahlberg, Dongchun Ni

Type I CRISPR-Cas systems typically rely on a two-step process to degrade DNA. First, an RNA-guided complex named Cascade identifies the complementary DNA target. The helicase-nuclease fusion enzyme Cas3 is then recruited in trans for processive DNA degrad ...

CELL PRESS2022

Development of multiplexed single-molecule imaging techniques to study chromatin invasion dynamics of chromatin effector proteins

Kristina Makasheva

DNA-binding proteins physically interact with the DNA and directly affect genomic functions. The eukaryotic genome is compacted into chromatin, limiting the DNA access to nuclear factors. In this Ph.D. thesis, I explored the dynamic mechanisms, that allow ...

EPFL2023

China lung cancer screening (CLUS) version 2.0 with new techniques implemented: Artificial intelligence, circulating molecular biomarkers and autofluorescence bronchoscopy

Jiancheng Yang

Objective: The present study, CLUS version 2.0, was conducted to evaluate the performance of new techniques in improving the implementation of lung cancer screening and to validate the efficacy of LDCT in reducing lung cancer-specific mortality in a high-r ...

ELSEVIER IRELAND LTD2023

The makings of TERRA R-loops at chromosome ends

Joachim Lingner, Marianna Feretzaki, Rita Valador Fernandes

Telomeres protect chromosome ends from nucleolytic degradation, uncontrolled recombination by DNA repair enzymes and checkpoint signaling, and they provide mechanisms for their maintenance by semiconservative DNA replication, telomerase and homologous reco ...

TAYLOR & FRANCIS INC2021

Challenging endings: How telomeres prevent fragility

Joachim Lingner, Galina Glousker

It has become apparent that difficulties to replicate telomeres concern not only the very ends of eukaryotic chromosomes. The challenges already start when the replication fork enters the telomeric repeats. The obstacles encountered consist mainly of nonca ...

WILEY2021

The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase(+) cells and telomeric recombination in ALT(+) cells

Joachim Lingner, Rita Valador Fernandes

Telomeres are the nucleoprotein structures at the ends of linear chromosomes. Telomeres are transcribed into long non-coding Telomeric Repeat-Containing RNA (TERRA), whose functions rely on its ability to associate with telomeric chromatin. The conserved T ...

OXFORD UNIV PRESS2023

Comparative Evaluation of Lipofectamine and Dendrimer for Transfection of Short RNA Into Human T47D and MCF-10A Cell Lines

Erfan Shirzadi

Purpose: Non-viral transfection approaches are extensively used in cancer therapy. The future of cancer therapy lies on targeted and efficient drug/gene delivery. The aim of this study was to determine the transfection yields of two commercially available ...

2023

A Role for Human DNA Polymerase λ in Alternative Lengthening of Telomeres

Joachim Lingner, Liuh-Yow Chen

Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addi ...

2021

Effect of the structural modification of Candesartan with Zinc on hypertension and left ventricular hypertrophy

Nikolaos Stergiopoulos, Augusto Martins Lima

Hypertension is the most common cause of left ventricular hypertrophy, contributing to heart failure progression. Candesartan (Cand) is an angiotensin receptor antagonist widely used for hypertension treatment. Structural modifications were previously perf ...

ELSEVIER2023

Relief of ParB autoinhibition by parS DNA catalysis and recycling of ParB by CTP hydrolysis promote bacterial centromere assembly

Paolo De Los Rios, Stefano Zamuner

Three-component ParABS systems are widely distributed factors for plasmid partitioning and chromosome segregation in bacteria. ParB acts as adaptor protein between the 16-base pair centromeric parS DNA sequences and the DNA segregation proteins ParA and Sm ...

AMER ASSOC ADVANCEMENT SCIENCE2021

Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8

Eftychia Kyriacou

Meiotic processes are potentially dangerous to genome stability and could be disastrous if activated in proliferative cells. Here we show that two key meiosis-defining proteins, the topoisomerase Spo11 (which forms double-strand breaks) and the meiotic coh ...

NATURE RESEARCH2021

Achieving high hybridization density at DNA biosensor surfaces using branched spacer and click chemistry

Sandrine Gerber, Mounir Driss Mensi, Perrine Agnes Edith Robin, Lucas Mayoraz, Alireza Kavand

The COVID-19 pandemic has highlighted the necessity to develop fast, highly sensitive and selective virus detection methods. Surface-based DNA-biosensors are interesting candidates for this purpose. Functionalization of solid substrates with DNA must be pr ...

2023

A field-capable rapid plant DNA extraction protocol using microneedle patches for botanical surveying and monitoring

Jonathan Selz, Sebastian Maerkl

PremiseA novel protocol for rapid plant DNA extraction using microneedles is proposed, which supports botanic surveys, taxonomy, and systematics. This protocol can be conducted in the field with limited laboratory skills and equipment. The protocol is vali ...

WILEY2023

m6A methylation potentiates cytosolic dsDNA recognition in a sequence-specific manner

Andrea Ablasser, Muhammet Fatih Gülen

Nucleic acid sensing through pattern recognition receptors is critical for immune recognition of microbial infections. Microbial DNA is frequently methylated at the N-6 position of adenines (m6A), a modification that is rare in mammalian host DNA. We show ...

ROYAL SOC2021

Tag, you're it: G-ICAT identifies p120-cysteine glutathionylation triggering E-cadherin destabilization

Kevin Timothy Fridianto, Yimon Aye

Current methods have limited ability in directly quantifying the extent of glutathionylation on specific proteincysteines. In this issue of Cell Chemical Biology, Ahn et al.1 report G-ICAT (glutathione-based isotope-coded affinity tag), aimed at addressing ...

CELL PRESS2023

The human telomeric proteome during telomere replication

Chih-Yi Gabriela Lin, Joachim Lingner, Aleksandra Vancevska, Thomas Frédéric Lunardi, Gérald Joseph Paul Lossaint

Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the sem ...

OXFORD UNIV PRESS2021