Publications associées à Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutS gamma complex

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

EPFL2024

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Natalya Katanayeva, Ruxandra-Andreea Lambuta, Juan Diaz Miyar, Giovanni Ciriello, Daniele Tavernari

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

NATURE PORTFOLIO2023

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

Preomic profile of BxPC-3 cells after treatment with BRC4

Andrea Cavalli

BRCA2 and RAD51 are two proteins that play a central role in homologous recombination (HR) and DNA double strand break (DSB) repair. BRCA2 assists RAD51 fibrillation and defibrillation through binding with its eight BRC repeats, with BRC4 being one of the ...

ELSEVIER2023

Elucidating and modulating regulatory pathways so as to reprogram the immunosuppressive tumor microenvironment for therapeutic benefit

Agnieszka Alicja Chryplewicz

Glioblastoma (GBM) is the most frequent and highly malignant form of brain cancer. New therapeutic regimens are urgently needed as GBM patients present with a minimal response to currently-approved therapies. The goal of this project is to identify new the ...

EPFL2023

Whole genome doubling promotes tumorigenesis through loss of chromatin segregation and compartment repositioning

Ruxandra-Andreea Lambuta

Whole genome doubling (WGD) events are drivers of genetic innovation across vertebrate evolution. While generally detrimental to mammalian organisms, WGDs are crucial in the development of various plants and fungi, as well as for the terminal differentiati ...

EPFL2023

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

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Elisa Oricchio, Natalya Katanayeva, Stephanie Jocelyne Sungalee, Ruxandra-Andreea Lambuta, Giovanni Ciriello, Daniele Tavernari

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is a ...

2021

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

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

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

Pulchelloid A, a sesquiterpene lactone from the Canadian prairie plant Gaillardia aristata inhibits mitosis in human cells

Tatiana Favez, Pierre Gönczy, Georgios Hatzopoulos

Background The Canadian prairie ecosystem presents a rich source of natural products from plants that are subjected to herbivory by grazing mammals. This type of ecological competition may contribute to the production of natural products of interest in cel ...

SPRINGER2021

Structural transitions and mechanochemical coupling in the nucleoprotein filament explain homology selectivity and Rad51 protein cooperativity in cellular DNA repair

Daniel Migliozzi

The nucleoprotein filament (NPF) is the fundamental element of homologous recombination (HR), a major mechanism for the repair of double-strand DNA breaks in the cell. The NPF is made of the damaged DNA strand surrounded by recombinase proteins, and its se ...

AMER PHYSICAL SOC2020

Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and vascular senescence

Johan Auwerx, Norman Lionel Moullan, Lei Chen

Long noncoding RNAs (lncRNAs) are emerging regulators of biological processes in the vessel wall; however, their role in atherosclerosis remains poorly defined. We used RNA sequencing to profile lncRNAs derived specifically from the aortic intima of Ldlr(- ...

AMER ASSOC ADVANCEMENT SCIENCE2020

Comprehensive analysis of PM20D1 QTL in Alzheimer's disease

Liliane Glauser, Johannes Gräff, Jose Vicente Sanchez Mut

Background Alzheimer's disease (AD) is a complex disorder caused by a combination of genetic and non-genetic risk factors. In addition, an increasing evidence suggests that epigenetic mechanisms also accompany AD. Genetic and epigenetic factors are not ind ...

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

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

SMCHD1 promotes ATM-dependent DNA damage signaling and repair of uncapped telomeres

Joachim Lingner, Verena Pfeiffer, Wareed Ahmed, Aleksandra Vancevska, Marianna Feretzaki

Structural maintenance of chromosomes flexible hinge domain-containing protein 1 (SMCHD1) has been implicated in X-chromosome inactivation, imprinting, and DNA damage repair, and mutations in SMCHD1 can cause facioscapulohumeral muscular dystrophy. More re ...

WILEY2020