Publications related to The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening

Resolving bacterial cell biology: from replisome dynamics to cell wall synthesis

Bacteria are ubiquitous single cellular organisms. Compared to eukaryotic cells, bacteria have two unique characteristics: the membrane-less nucleoid and the cell wall built of peptidoglycan (PG). In most bacteria, a single circular chromosome is compacted ...

EPFL2024

Chromosome organization shapes replisome dynamics in Caulobacter crescentus

Suliana Manley, Laurent Casini, Chen Zhang

DNA replication in bacteria takes place on highly compacted chromosomes, where segregation, transcription, and repair must occur simultaneously. Within this dynamic environment, colocalization of sister replisomes has been observed in many bacterial specie ...

Nature Portfolio2024

Regulation and impact of TERRA R-loops at human telomeres

Rita Valador Fernandes

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

Telomere protection against oxidative stress

Thu Trang Nguyen

Telomeres are nucleoprotein structures at the ends of linear chromosomes, being essential for the maintenance of genomic integrity. Telomeres have a unique structure which distinguishes chromosome termini from DNA damage sites. Shelterin complexes are the ...

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

C2CAplus: A One-Pot Isothermal Circle-to-Circle DNA Amplification System

Sebastian Maerkl, Laura Sophie Grasemann

Rolling circle amplification (RCA) is a widely used DNA amplification method that uses circular template DNA as input and produces multimeric, linear single- or double-stranded DNA. Circle-to-circle amplification (C2CA) has further expanded this method by ...

Amer Chemical Soc2023

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

TFIIH moonlighting at telomeres

Joachim Lingner, Galina Glousker

Although telomeres are essential for chromosome stability, they represent fragile structures in our genome. Telomere shortening occurs during aging in cells lacking telomerase due to the end replication problem. In addition, recent work uncovered that the ...

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT2022

Natural competence of the pathogen Acinetobacter baumannii: an elusive phenomenon

Nina Vesel

Natural competence for transformation is an important driver of horizontal DNA exchange between different organisms. This can result in accumulation of dangerous genetic features, such as antibiotic resistance genes, in a single organism. One example of an ...

EPFL2022

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

The human telomeric proteome during telomere replication

Joachim Lingner, Aleksandra Vancevska, Thomas Frédéric Lunardi, 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

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

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

Towards an artificial cell: Development of a system which self-regenerates the protein components of the PURE system in microfluidic reactors

Barbora Lavickova

Thanks to recent advancements in synthetic biology, the dream of creating a synthetic cell has become feasible. However, due to its inherent complexity, one of the fundamental functions of all living systems, i.e., self-replication, remains to be introduce ...

EPFL2021

High throughput screening identifies SOX2 as a super pioneer factor that inhibits DNA methylation maintenance at its binding sites

Ludovica Vanzan

Binding of mammalian transcription factors (TFs) to regulatory regions is hindered by chromatin compaction and DNA methylation of their binding sites. Nevertheless, pioneer transcription factors (PFs), a distinct class of TFs, have the ability to access nu ...

Nature Research2021

Coordination between cell growth, division and chromosome replication cycles in mycobacteria

Gaëlle Madeleine Vuaridel

Propagation of microorganisms is based on three fundamental processes: cell growth, DNA replication, and cell division. Although important for antibacterial drug development, these processes are poorly understood in Actinobacteria, a medically important ph ...

EPFL2021

Dynamic Chromatin Invasion and Remodeling by the Transcription Factor Rap1

Maxime Nicolas Mivelaz

Pioneer transcription factors (PTF) are a subset of transcription factors with nucleosome-binding properties allowing them to bind specific sequences in condensed chromatin. Although the biological functions of PTFs including target genes and epigenetic ch ...

EPFL2021

RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops

Joachim Lingner, Thomas Frédéric Lunardi, Marianna Feretzaki, Rita Valador Fernandes

Telomeres-repeated, noncoding nucleotide motifs and associated proteins that are found at the ends of eukaryotic chromosomes-mediate genome stability and determine cellular lifespan1. Telomeric-repeat-containing RNA (TERRA) is a class of long noncoding RNA ...

2020

Requirements for DNA bubble structure for efficient cleavage by helix-two-turn-helix DNA glycosylases

Kristina Makasheva

Oxidative DNA lesions, constantly generated by both endogenous and environmentally induced reactive oxygen species, are removed via the base excision repair pathway. In bacteria, Fpg and Nei DNA glycosylases, belonging to the helix-two-turn-helix (H2TH) st ...

2020

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

Joachim Lingner, Wareed Ahmed

Telomeres are prone to damage inflicted by reactive oxygen species (ROS). Oxidized telomeric DNA and nucleotide substrates inhibit telomerase, causing telomere shortening. In addition, ROS can induce telomeric single-strand DNA breaks (SSBs). The peroxired ...

2020