Publications associées à Caretaker gene

Identification and characterization of proteins that protect human telomeres from fragility

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

Next-generation cancer organoids

Matthias Lütolf, Nicolas Antoine Vincent Broguiere

Organotypic models of patient-specific tumours are revolutionizing our understanding of cancer heterogeneity and its implications for personalized medicine. These advancements are, in part, attributed to the ability of organoid models to stably preserve ge ...

NATURE PORTFOLIO2022

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

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

Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and Housekeeping Genes in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Andrej Benjak, Nina Theres Odermatt

Tight control of gene expression is crucial for Mycobacterium tuberculosis to adapt to the changing environments encountered when infecting or exiting human cells. While three nucleoid associated proteins (NAPs) EspR, HupB and Lsr2 have been investigated, ...

Nature Research2018

KAP1 facilitates reinstatement of heterochromatin after DNA replication

Didier Trono, Suk Min Jang, Priscilla Turelli, Sandra Eloise Kjeldsen, Julien Léonard Duc, Annamaria Kauzlaric, Andrea Coluccio, Julien Paul André Pontis, Benjamin Rauwel, Geneviève Almouzni

During cell division, maintenance of chromatin features from the parental genome requires their proper establishment on its newly synthetized copy. The loss of epigenetic marks within heterochromatin, typically enriched in repetitive elements, endangers ge ...

2018

The telomeric DNA damage response occurs in the absence of chromatin decompaction

Joachim Lingner, Suliana Manley, Verena Pfeiffer, Aleksandra Vancevska, Kyle Michael Douglass

Telomeres are specialized nucleoprotein structures that protect chromosome ends from DNA damage response (DDR) and DNA rearrangements. The telomeric shelterin protein TRF2 suppresses the DDR, and this function has been attributed to its abilities to trigge ...

Cold Spring Harbor Laboratory2017

Telomere functions grounding on TERRA firma

Joachim Lingner

Long noncoding telomeric repeat-containing RNAs TERRAs - are transcribed in a regulated manner from telomeres throughout eukaryotes. TERRA molecules consist of chromosome end-specific subtelomeric sequences and telomeric repeats at their 3' ends. Recent wo ...

Elsevier Science London2015

Metabolic Needs and Capabilities of Toxoplasma gondii through Combined Computational and Experimental Analysis

Vassily Hatzimanikatis, Stepan Tymoshenko, Rebecca Oppenheim, Jens Nielsen, Dominique Soldati-Favre

Toxoplasma gondii is a human pathogen prevalent worldwide that poses a challenging and unmet need for novel treatment of toxoplasmosis. Using a semi-automated reconstruction algorithm, we reconstructed a genome-scale metabolic model, ToxoNet1. The reconstr ...

Public Library Science2015

Transposable elements and their KRAB/KAP1 controllers broadly regulate transcription in adult human cells

Flavia Marzetta

KAP1 is a universal corepressor for the large family of KRAB-ZFP proteins that coordinates epigenetic silencing of endogenous retroelements (EREs) during early embryonic development. This process is essential not just to prevent replication of EREs, but al ...

EPFL2015

Nuclear Factor I genomic binding associates with chromatin boundaries

Giovanni Dietler, Giovanna Ambrosini, Philipp Bucher, Nicolas Mermod, Petar Pjanic, Jan Kerschgens, Armelle Gaussin

Background: The Nuclear Factor I (NFI) family of DNA binding proteins (also called CCAAT box transcription factors or CTF) is involved in both DNA replication and gene expression regulation. Using chromatin immuno-precipitation and high throughput sequenci ...

BioMed Central2013

MicroRNA-mediated control of macrophages and its implications for cancer

Michele De Palma, Mario Leonardo Squadrito, Martin Etzrodt

Deregulation of microRNAs (miRNAs) can drive oncogenesis, tumor progression, and metastasis by acting cell-autonomously in cancer cells. However, solid tumors are also infiltrated by large amounts of non-neoplastic stromal cells, including macrophages, whi ...

Elsevier Sci Ltd2013

Isolation and Characterisation of Regulators of the Septation Initiation Network Regulators in Fission Yeast

Anupama Goyal

The septation initiation network (SIN) in Schizosaccharomyces pombe regulates cytokinesis. Cdc7p encodes the first kinase in the core SIN pathway. In this study, I performed a genetic screen to identify novel regulators of the SIN pathway by isolating spon ...

EPFL2012

Insight into the Regulation of Telomerase Access to Telomeres by Shelterin Proteins

Elena Aritonovska

Recruitment to telomeres is a pivotal step in the function and regulation of human telomerase. Impaired telomerase function can lead to premature organismal aging, development of cancer and multisystem disorders such as dyskeratosis congenita. Telomerase a ...

EPFL2011

FcRgamma activation regulates inflammation-associated squamous carcinogenesis

Michele De Palma, Ferdinando Pucci

Chronically activated leukocytes recruited to premalignant tissues functionally contribute to cancer development; however, mechanisms underlying pro- versus anti-tumor programming of neoplastic tissues by immune cells remain obscure. Using the K14-HPV16 mo ...

2010

Gene expression profiling in cells with enhanced gamma-secretase activity

Patrick Fraering, Alexandra Marie-Isabelle Karoline Brigitte Magold

BACKGROUND: Processing by gamma-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a div ...

Public Library of Science2009

The double life of UPF1 in RNA and DNA stability pathways

Joachim Lingner

The DNA and RNA helicase UPF1 is well known for its central role in Nonsense Mediated RNA Decay (NMD), which promotes degradation of mRNAs containing premature stop codons. However, we have recently demonstrated that human UPF1 is also essential for DNA re ...

2006