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Concept

Genome instability

Publications associées (28)

Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos

Fides Zenk

Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 ( ...

Springernature2024

Androgen Receptor Signaling in in vivo models of Estrogen Receptor-positive Breast Cancer and Normal Breast Epithelium

Andrea Agnoletto

Steroid hormone receptors (HRs) are ligand-activated transcription factors that play a pivotal role in breast development and carcinogenesis. It is well established that estrogen receptor (ER) signaling is a major proliferative driver in estrogen receptor ...

EPFL2024

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

Whole-genome doubling drives oncogenic loss of chromatin segregation

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

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

KRAB zinc finger proteins link heterochromatin maintenance to replicative stress and inflammation in diffuse large B-cell lymphoma

Filipe Amândio Brandão Sanches Vong Martins

Genomic instability enhances cancer progression by favoring clonal diversity, yet uncontrolled replicative stress can lead to mitotic catastrophe and inflammatory responses promoting immune rejection. KRAB-containing zinc finger proteins (KZFPs) are epigen ...

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

Genomic Instability Profiles at the Single Cell Level in Mouse Colorectal Cancers of Defined Genotypes

Jörg Hülsken, Maxim Norkin

The genomes of many human CRCs have been sequenced, revealing a large number of genetic alterations. However, the molecular mechanisms underlying the accumulation of these alterations are still being debated. In this study, we examined colorectal tumours t ...

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

Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells

Sebastian Martin Waszak, Ruxandra-Andreea Lambuta

TP53 deficiency is the most common alteration in cancer; however, this alone is typically insufficient to drive tumorigenesis. To identify genes promoting tumorigenesis in combination with TP53 deficiency, we perform genome-wide CRISPR-Cas9 knockout screen ...

2020

STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pathway

Friedrich Beermann

Metastatic melanoma is hallmarked by its ability of phenotype switching to more slowly proliferating, but highly invasive cells. Here, we tested the impact of signal transducer and activator of transcription 3 (STAT3) on melanoma progression in association ...

SPRINGERNATURE2021

Advanced technological tools to study multidrug resistance in cancer

Sandor Kasas

The complexity of cancer biology and its clinical manifestation are driven by genetic, epigenetic, transcriptomic, proteomic and metabolomic alterations, supported by genomic instability as well as by environmental conditions and lifestyle factors. Althoug ...

CHURCHILL LIVINGSTONE2020

Improving visible light photocatalytic inactivation of E. coli by inducing highly efficient radical pathways through peroxymonosulfate activation using 3-D, surface-enhanced, reduced graphene oxide (rGO) aerogels

César Pulgarin, Stefanos Giannakis

In this work, we synthesized highly porous reduced graphene oxide foams, presenting augmented antibacterial activity in presence/absence of peroxymonosulfate (PMS). To date, this is the first investigation of photocatalytic PMS disinfection by 3D-rGO mater ...

ELSEVIER SCIENCE SA2020

Roles of Epigenetic Dysregulation in Cancer Progression and Metastasis

Mohammad Sadegh Saghafinia

Nearly all the cells of an organism share the same DNA sequence or genome, and yet they show different phenotypes and carry out different functions. This diversity is made possible by a verity of molecular modifications acting on the DNA sequence that coll ...

EPFL2020

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

CSL controls telomere maintenance and genome stability in human dermal fibroblasts

Joachim Lingner, Thomas Frédéric Lunardi, Paris Jafari

Genomic instability is a hallmark of cancer. Whether it also occurs in Cancer Associated Fibroblasts (CAFs) remains to be carefully investigated. Loss of CSL/RBP-J kappa, the effector of canonical NOTCH signaling with intrinsic transcription repressive fun ...

Springer2019

Functional analysis of the telomeric long non-coding RNA TERRA

Patricia Renck Nunes

Telomeres are nucleoprotein structures present in the end of linear chromosomes. In humans, a core complex of 6 proteins cap and protect the chromosome ends from being recognized as double-strand breaks and eliciting unwanted DNA damage and repair response ...

EPFL2019

Premature activation of Cdk1 leads to mitotic events in S phase and embryonic lethality

João Pedro de Matos Rodrigues, Patricia Renck Nunes

Cell cycle regulation, especially faithful DNA replication and mitosis, are crucial to maintain genome stability. Cyclin-dependent kinase (CDK)/cyclin complexes drive most processes in cellular proliferation. In response to DNA damage, cell cycle surveilla ...

Springer2019

Differences in viral disinfection mechanisms as revealed by quantitative transfection of Echovirus 11 genomes

Urs von Gunten, Tamar Kohn, Jason Robert Torrey

Virus inactivation mechanisms can be elucidated by methods which measure the loss of specific virus functionality (e.g., host attachment, genome internalization, genome replication). Genome functionality is frequently assessed by PCR-based methods, which a ...

2019

The telomeric DNA damage response: Insights into telomere compaction and identification of novel damage signaling factors

Aleksandra Vancevska

Telomeres are dynamic nucleo-protein structures capping the ends of all eukaryotic chromosomes. Together with telomerase, they counteract replication-dependent telomere attrition. Additionally, they disguise the linear ends of the chromosome from the DNA d ...

EPFL2018

Polyphenic trait promotes liver cancer in a model of epigenetic instability

Didier Trono, Sandra Eloise Kjeldsen, Alessandra Piersigilli, Evaristo Jose Planet Letschert, Marco Cassano, Suk Min Jang

Hepatocellular carcinoma (HCC) represents the fifth most common form of cancer worldwide and carries a high mortality rate due to lack of effective treatment. Males are eight times more likely to develop HCC than females, an effect largely driven by sex ho ...

Wiley-Blackwell2017