Publications related to Okazaki fragments

Regulation and impact of TERRA R-loops at human telomeres

Telomeres are the nucleoprotein structures found at the ends of linear chromosomes. They ensure that the termini of chromosomes are not inappropriately recognized as sites of DNA damage, and are therefore crucial for genome stability. In spite of the heter ...

EPFL2023

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

Polydimethylsiloxane microstructure-induced acoustic streaming for enhanced ultrasonic DNA fragmentation on a microfluidic chip

Martinus Gijs, Thomas Lehnert, Lin Sun

Next-generation sequencing (NGS) is an essential technology for DNA identification in genomic research. DNA fragmentation is a critical step for NGS and doing this on-chip is of great interest for future integrated genomic solutions. Here we demonstrate fa ...

ROYAL SOC CHEMISTRY2022

Identification and characterization of proteins that protect human telomeres from fragility

Anna Christina Näger

Difficulties to replicate telomeres - the ends of our chromosomes - can cause telomere shortening and genome instability. These difficulties are due to the repetitive DNA sequence and distinct structures at telomeres that challenge the semi-conservative DN ...

EPFL2022

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 human telomeric proteome during telomere replication

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

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

Redox Properties of Native and Damaged DNA from Mixed Quantum Mechanical/Molecular Mechanics Molecular Dynamics Simulations

Ursula Röthlisberger, Ivano Tavernelli, Polydefkis Diamantis

The redox properties of two large DNA fragments composed of 39 base pairs, differing only by an 8-oxoguanine (8oxoG) defect replacing a guanine (G), were investigated in physiological conditions using mixed quantum mechanical/molecular mechanical (QM/MM) m ...

AMER CHEMICAL SOC2020

Human shelterin protein POT1 prevents severe telomere instability induced by homology-directed DNA repair

Joachim Lingner, Galina Glousker, Anna-Sophia Briod

The evolutionarily conserved POT1 protein binds single-stranded G-rich telomeric DNA and has been implicated in contributing to telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through g ...

WILEY2020

Generation of a Large Peptide Phage Display Library by Self-Ligation of Whole-Plasmid PCR Product

Christian Heinis, Xudong Kong, Vanessa Carle, Cristina Diaz Perlas, Kaycie Marie Butler

The success of phage display, used for developing target-specific binders based on peptides and proteins, depends on the size and diversity of the library screened, but generating large libraries of phage-encoded polypeptides remains challenging. New pepti ...

2020

Crosstalk between Drp1 phosphorylation sites during mitochondrial dynamics and metabolic adaptation

Miriam Valera Alberni

Mitochondria are highly dynamics organelles that undergo coordinated cycles of fission and fusion, referred to as mitochondrial dynamics. Mitochondrial dynamics regulate mitochondrial bioenergetics and allow cells to adapt to changing cellular stresses and ...

EPFL2020

PaRiS: Causally Consistent Transactions with Non-blocking Reads and Partial Replication

Willy Zwaenepoel, Diego Didona, Kristina Spirovska

Geo-replicated data platforms are at the backbone of several large-scale online services. Transactional Causal Consistency (TCC) is an attractive consistency level for building such platforms. TCC avoids many anomalies of eventual consistency, eschews the ...

2019

PaRiS: Causally Consistent Transactions with Non-blocking Reads and Partial Replication

Willy Zwaenepoel, Diego Didona, Kristina Spirovska

Geo-replicated data platforms are the backbone of several large-scale online services. Transactional Causal Consistency (TCC) is an attractive consistency level for building such platforms. TCC avoids many anomalies of eventual consistency, eschews the syn ...

IEEE COMPUTER SOC2019

RADX: A novel single-stranded DNA-binding protein regulating telomere recombination

Anna-Sophia Briod

Telomeres are specialized nucleoprotein structures present at the ends of linear chromosome. The telomeric DNA part is comprised of 5-15 kilo base pairs of double stranded TTAGGG repeats and it contains at the 3' end a single-stranded G-rich overhang of 50 ...

EPFL2019

Fixed DNA Molecule Arrays for High-Throughput Single DNA-Protein Interaction Studies

Vytautas Navikas

The DNA Curtains assay is a recently developed experimental platform for protein-DNA interaction studies at the single-molecule level that is based on anchoring and alignment of DNA fragments. The DNA Curtains so far have been made by using chromium barrie ...

AMER CHEMICAL SOC2019

Vertical Ionization Energies and Electron Affinities of Native and Damaged DNA Bases, Nucleotides, and Pairs from Density Functional Theory Calculations: Model Assessment and Implications for DNA Damage Recognition and Repair

Ursula Röthlisberger, Ivano Tavernelli, Polydefkis Diamantis

To assess the effect of an 8-oxoguanine (8OG) defect base on the vertical ionization energies (VIEs) and electron affinities (VEAs) of DNA, density functional theory calculations were carried out for native and defect DNA bases and nucleotides, as well as ...

2019

Beyond silence : a functional and evolutionary study of KRAB zinc finger proteins

Pierre-Yves Joseph Laurent Helleboid

Transposable elements (TEs) are genetic units capable of spreading within the genomes of their host. TEs contribute a readily recognizable 45% of the human DNA, reflecting in part their co-option for some as source of protein-coding sequences, for others a ...

EPFL2019

Telomeric states in cancer development

Jana Majerská

Telomere dysfunction can unleash genome instability or permanently arrest cell proliferation, and thereby contribute to the processes of cancer and aging. Proper telomere function relies on many proteins that form part of its structure. Some telomeric prot ...

EPFL2018

Cell lineage tracing in human tissues using somatic mitochondrial mutations

Paul Refinetti

Lineage tracing is a basic concept in developmental biology, as well as diseases related to organ development. A reliable method to track cell lineages in human tissues has the potential to greatly contribute to the fields of oncogenesis, tissue renewal, a ...

EPFL2017

On the statistical physics of chains and rods, with application to multi-scale sequence-dependent DNA modelling

Alexandre Emmanuel Grandchamp

The complex mechanisms involved in cellular processes have been increasingly understood this past century and the central role of the DNA molecule has been recognized. The base pair sequence along a DNA fragment is observed not only to encode the genomic i ...

EPFL2016

Protein ruthenation and DNA alkylation: chlorambucil-functionalized RAPTA complexes and their anticancer activity

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov, Olivier Pierre Zava

Chemotherapeutics for the treatment of tumorigenic conditions that feature novel modes of action are highly sought after to overcome the limitations of current chemotherapies. Herein, we report the conjugation of the alkylating agent chlorambucil to the RA ...

2015