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  1. Article ; Online: The Dynamic Behavior of Chromatin in Response to DNA Double-Strand Breaks.

    García Fernández, Fabiola / Fabre, Emmanuelle

    Genes

    2022  Volume 13, Issue 2

    Abstract: The primary functions of the eukaryotic nucleus as a site for the storage, retrieval, and replication of information require a highly dynamic chromatin organization, which can be affected by the presence of DNA damage. In response to double-strand breaks ...

    Abstract The primary functions of the eukaryotic nucleus as a site for the storage, retrieval, and replication of information require a highly dynamic chromatin organization, which can be affected by the presence of DNA damage. In response to double-strand breaks (DSBs), the mobility of chromatin at the break site is severely affected and, to a lesser extent, that of other chromosomes. The how and why of such movement has been widely studied over the last two decades, leading to different mechanistic models and proposed potential roles underlying both local and global mobility. Here, we review the state of the knowledge on current issues affecting chromatin mobility upon DSBs, and highlight its role as a crucial step in the DNA damage response (DDR).
    MeSH term(s) Chromatin/genetics ; DNA ; DNA Breaks, Double-Stranded ; DNA Damage ; DNA Repair/genetics
    Chemical Substances Chromatin ; DNA (9007-49-2)
    Language English
    Publishing date 2022-01-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13020215
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  2. Article ; Online: 3D Genome Organization: Causes and Consequences for DNA Damage and Repair.

    Carré-Simon, Ànnia / Fabre, Emmanuelle

    Genes

    2021  Volume 13, Issue 1

    Abstract: The inability to repair damaged DNA severely compromises the integrity of any organism. In eukaryotes, the DNA damage response (DDR) operates within chromatin, a tightly organized DNA-histone complex in a non-random manner within the nucleus. Chromatin ... ...

    Abstract The inability to repair damaged DNA severely compromises the integrity of any organism. In eukaryotes, the DNA damage response (DDR) operates within chromatin, a tightly organized DNA-histone complex in a non-random manner within the nucleus. Chromatin thus orchestrates various cellular processes, including repair. Here, we examine the chromatin landscape before, during, and after the DNA damage, focusing on double strand breaks (DSBs). We study how chromatin is modified during the repair process, not only around the damaged region (in
    MeSH term(s) Chromatin/genetics ; DNA Damage ; DNA Repair ; Genome, Human ; Humans
    Chemical Substances Chromatin
    Language English
    Publishing date 2021-12-21
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13010007
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  3. Article: Performance Characteristics of Oncomine Focus Assay for Theranostic Analysis of Solid Tumors, A (21-Months) Real-Life Study.

    Bamba-Funck, Jessica / Fabre, Emmanuelle E / Kambouchner, Marianne / Schischmanoff, Olivier

    Diagnostics (Basel, Switzerland)

    2023  Volume 13, Issue 5

    Abstract: Next generation sequencing analysis is crucial for therapeutic decision in various solid tumor contexts. The sequencing method must remain accurate and robust throughout the instrument lifespan allowing the biological validation of patients' results. ... ...

    Abstract Next generation sequencing analysis is crucial for therapeutic decision in various solid tumor contexts. The sequencing method must remain accurate and robust throughout the instrument lifespan allowing the biological validation of patients' results. This study aims to evaluate the long-term sequencing performances of the Oncomine Focus assay kit allowing theranostic DNA and RNA variants detection on the Ion S5XL instrument. We evaluated the sequencing performances of 73 consecutive chips over a 21-month period and detailed the sequencing data obtained from both quality controls and clinical samples. The metrics describing sequencing quality remained stable throughout the study. We showed that an average of 11 × 10
    Language English
    Publishing date 2023-03-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics13050937
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  4. Article: The Dynamic Behavior of Chromatin in Response to DNA Double-Strand Breaks

    García Fernández, Fabiola / Fabre, Emmanuelle

    Genes. 2022 Jan. 25, v. 13, no. 2

    2022  

    Abstract: The primary functions of the eukaryotic nucleus as a site for the storage, retrieval, and replication of information require a highly dynamic chromatin organization, which can be affected by the presence of DNA damage. In response to double-strand breaks ...

    Abstract The primary functions of the eukaryotic nucleus as a site for the storage, retrieval, and replication of information require a highly dynamic chromatin organization, which can be affected by the presence of DNA damage. In response to double-strand breaks (DSBs), the mobility of chromatin at the break site is severely affected and, to a lesser extent, that of other chromosomes. The how and why of such movement has been widely studied over the last two decades, leading to different mechanistic models and proposed potential roles underlying both local and global mobility. Here, we review the state of the knowledge on current issues affecting chromatin mobility upon DSBs, and highlight its role as a crucial step in the DNA damage response (DDR).
    Keywords DNA ; DNA damage ; chromatin
    Language English
    Dates of publication 2022-0125
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13020215
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Chromatin mobility upon DNA damage: state of the art and remaining questions.

    Zimmer, Christophe / Fabre, Emmanuelle

    Current genetics

    2018  Volume 65, Issue 1, Page(s) 1–9

    Abstract: Chromosome organization and chromatin mobility are central to DNA metabolism. In particular, it has been recently shown by several labs that double strand breaks (DSBs) in yeast induce a change in chromatin mobility at the site of the damage. ... ...

    Abstract Chromosome organization and chromatin mobility are central to DNA metabolism. In particular, it has been recently shown by several labs that double strand breaks (DSBs) in yeast induce a change in chromatin mobility at the site of the damage. Intriguingly, DSB also induces a global mobility of the genome, at others, potentially undamaged positions. How mobility is regulated and what are the functional outcomes of these global changes in chromatin dynamics are, however, not yet fully understood. We present the current state of knowledge in light of the recent literature and discuss some perspectives opened by these discoveries towards genome stability.
    MeSH term(s) Animals ; Chromatin/genetics ; Chromatin/metabolism ; DNA/genetics ; DNA/metabolism ; DNA Breaks, Double-Stranded ; DNA Repair ; Genomic Instability ; Histones/metabolism ; Humans ; Phosphorylation ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism
    Chemical Substances Chromatin ; Histones ; DNA (9007-49-2)
    Language English
    Publishing date 2018-06-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 282876-5
    ISSN 1432-0983 ; 0172-8083
    ISSN (online) 1432-0983
    ISSN 0172-8083
    DOI 10.1007/s00294-018-0852-6
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2586: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
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  6. Article: Successful sequential tyrosine kinase inhibitors to overcome a rare compound of EGFR exon 18-18 and EGFR amplification: A case report.

    Wang, Pascal / Fabre, Emmanuelle / Martin, Antoine / Chouahnia, Kader / Benabadji, Ambre / Matton, Lise / Duchemann, Boris

    Frontiers in oncology

    2022  Volume 12, Page(s) 918855

    Abstract: Background: New mutational detection techniques like next-generation sequencing have resulted in an increased number of cases with uncommon mutation and compound mutations [3%-14% of all epidermal growth factor receptor (EGFR) mutations]. In rare exon ... ...

    Abstract Background: New mutational detection techniques like next-generation sequencing have resulted in an increased number of cases with uncommon mutation and compound mutations [3%-14% of all epidermal growth factor receptor (EGFR) mutations]. In rare exon 18 mutations (3%-6%), G719X and E709X represent the majority, but CMut associating these exon 18 points mutations are even rarer, making the understanding of the impact of epidermal growth factor receptor tyrosine kinase inhibitors still limited. Three generations of EGFR tyrosine kinase inhibitors (TKIs) are available to target EGFR mutations, but according to the types of mutations, the sensitivity to TKI is different. Afatinib, osimertinib, and neratinib have showed some effectiveness in single exon 18, but no report has precisely described their efficiency and acquired mechanism of resistance in a CMut of exon 18-18 (G719A and E709A).
    Case presentation: We report a case of a 26-year-old woman with bilateral advanced adenocarcinoma of the lung harboring a compound mutation associating G719A and E709A in exon 18, who developed an EGFR amplification as resistance mechanism to osimertinib. She presented a significant clinical and morphological response under sequential TKIs treatment (afatinib, osimertinib, and then neratinib).
    Conclusion: A non-small cell lung cancer (NSCLC) with rare compound mutation exon 18-exon 18 (G719A and E709A) and EGFR amplification can be overcome with adapted sequential second- and third-generation TKIs. This report has potential implications in guiding decisions for the treatment of these rare EGFR mutations.
    Language English
    Publishing date 2022-07-25
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.918855
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  7. Article ; Online: Reconstituting the Interaction Between Purified Nuclei and Microtubule Network.

    Agsu, Gökçe / Gaillard, Jérémie / Cadot, Bruno / Blanchoin, Laurent / Fabre, Emmanuelle / Théry, Manuel

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2430, Page(s) 385–399

    Abstract: The nucleus is the stiffest organelle in the cell. Several morphogenetic processes depend on its deformation such as cell migration, cell differentiation, or senescence. Recent studies have revealed various mechanisms involved in the regulation of ... ...

    Abstract The nucleus is the stiffest organelle in the cell. Several morphogenetic processes depend on its deformation such as cell migration, cell differentiation, or senescence. Recent studies have revealed various mechanisms involved in the regulation of nucleus stiffness and deformation. The implication of chromatin swelling, lamin density, actin filament, and microtubule network revealed that nucleus shape is the outcome of a fine balance between various sources of external forces and numerous means of internal resistance. In adherent cells, the actin network is the dominant player in external force production, whereas in nonadherent cells microtubules seem to take over. It is therefore important to set up reconstitution assays in order to decipher the exact contribution of each player in this mechanical balance. In this method, we describe a nucleus purification protocol that is suitable for nonadherent cells. We also show that purified nuclei can interact with microtubules and that nuclei purified from distinct cell types get differentially wrapped into the array of microtubules. A combination with a microtubule gliding assay offers the possibility to counterbalance the binding to the nucleus membrane by active motor-based forces pulling on microtubules. So this protocol allows an in-depth study of microtubule-nucleus interactions in vitro.
    MeSH term(s) Actin Cytoskeleton/metabolism ; Actins/metabolism ; Cell Nucleus/metabolism ; Mechanical Phenomena ; Microtubules/metabolism
    Chemical Substances Actins
    Language English
    Publishing date 2022-04-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1983-4_25
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  8. Article ; Online: Inducible degradation of the Drosophila Mediator subunit Med19 reveals its role in regulating developmental but not constitutively-expressed genes.

    Jullien, Denis / Guillou, Emmanuelle / Bernat-Fabre, Sandra / Payet, Adeline / Bourbon, Henri-Marc G / Boube, Muriel

    PloS one

    2022  Volume 17, Issue 11, Page(s) e0275613

    Abstract: The multi-subunit Mediator complex plays a critical role in gene expression by bridging enhancer-bound transcription factors and the RNA polymerase II machinery. Although experimental case studies suggest differential roles of Mediator subunits, a ... ...

    Abstract The multi-subunit Mediator complex plays a critical role in gene expression by bridging enhancer-bound transcription factors and the RNA polymerase II machinery. Although experimental case studies suggest differential roles of Mediator subunits, a comprehensive view of the specific set of genes regulated by individual subunits in a developing tissue is still missing. Here we address this fundamental question by focusing on the Med19 subunit and using the Drosophila wing imaginal disc as a developmental model. By coupling auxin-inducible degradation of endogenous Med19 in vivo with RNA-seq, we got access to the early consequences of Med19 elimination on gene expression. Differential gene expression analysis reveals that Med19 is not globally required for mRNA transcription but specifically regulates positively or negatively less than a quarter of the expressed genes. By crossing our transcriptomic data with those of Drosophila gene expression profile database, we found that Med19-dependent genes are highly enriched with spatially-regulated genes while the expression of most constitutively expressed genes is not affected upon Med19 loss. Whereas globally downregulation does not exceed upregulation, we identified a functional class of genes encoding spatially-regulated transcription factors, and more generally developmental regulators, responding unidirectionally to Med19 loss with an expression collapse. Moreover, we show in vivo that the Notch-responsive wingless and the E(spl)-C genes require Med19 for their expression. Combined with experimental evidences suggesting that Med19 could function as a direct transcriptional effector of Notch signaling, our data support a model in which Med19 plays a critical role in the transcriptional activation of developmental genes in response to cell signaling pathways.
    MeSH term(s) Animals ; Drosophila/genetics ; Imaginal Discs ; Transcriptional Activation ; RNA Polymerase II ; Transcription Factors/genetics
    Chemical Substances RNA Polymerase II (EC 2.7.7.-) ; Transcription Factors
    Language English
    Publishing date 2022-11-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0275613
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A second case of multisystem inflammatory syndrome associated with SARS-CoV-2 in a liver-transplanted child.

    Duvant, Pauline / Roquelaure, Bertrand / Morand, Aurélie / Bosdure, Emmanuelle / Garaix, Florentine / Zandotti, Christine / Fabre, Alexandre

    Pediatric transplantation

    2021  Volume 26, Issue 1, Page(s) e14116

    MeSH term(s) COVID-19/complications ; Child ; Humans ; Intensive Care Units, Pediatric ; Liver ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome
    Language English
    Publishing date 2021-08-20
    Publishing country Denmark
    Document type Editorial ; Comment
    ZDB-ID 1390284-2
    ISSN 1399-3046 ; 1397-3142
    ISSN (online) 1399-3046
    ISSN 1397-3142
    DOI 10.1111/petr.14116
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4947: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  10. Article: 3D Genome Organization: Causes and Consequences for DNA Damage and Repair

    Carré-Simon, Ànnia / Fabre, Emmanuelle

    Genes. 2021 Dec. 21, v. 13, no. 1

    2021  

    Abstract: The inability to repair damaged DNA severely compromises the integrity of any organism. In eukaryotes, the DNA damage response (DDR) operates within chromatin, a tightly organized DNA–histone complex in a non-random manner within the nucleus. Chromatin ... ...

    Abstract The inability to repair damaged DNA severely compromises the integrity of any organism. In eukaryotes, the DNA damage response (DDR) operates within chromatin, a tightly organized DNA–histone complex in a non-random manner within the nucleus. Chromatin thus orchestrates various cellular processes, including repair. Here, we examine the chromatin landscape before, during, and after the DNA damage, focusing on double strand breaks (DSBs). We study how chromatin is modified during the repair process, not only around the damaged region (in cis), but also genome-wide (in trans). Recent evidence has highlighted a complex landscape in which different chromatin parameters (stiffness, compaction, loops) are transiently modified, defining “codes” for each specific stage of the DDR. We illustrate a novel aspect of DDR where chromatin modifications contribute to the movement of DSB-damaged chromatin, as well as undamaged chromatin, ensuring the mobilization of DSBs, their clustering, and their repair processes.
    Keywords DNA ; DNA damage ; chromatin ; eukaryotic cells ; landscapes
    Language English
    Dates of publication 2021-1221
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13010007
    Database NAL-Catalogue (AGRICOLA)

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