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  1. Article ; Online: The DNA damage response in the chromatin context: A coordinated process.

    Dabin, Juliette / Mori, Margherita / Polo, Sophie E

    Current opinion in cell biology

    2023  Volume 82, Page(s) 102176

    Abstract: In the cell nucleus, DNA damage signaling and repair machineries operate on a chromatin substrate, the integrity of which is critical for cell function and viability. Here, we review recent advances in deciphering the tight coordination between chromatin ...

    Abstract In the cell nucleus, DNA damage signaling and repair machineries operate on a chromatin substrate, the integrity of which is critical for cell function and viability. Here, we review recent advances in deciphering the tight coordination between chromatin maintenance and the DNA damage response (DDR). We discuss how the DDR impacts chromatin marks, organization and mobility, and, in turn, how chromatin alterations actively contribute to the DDR, providing additional levels of regulation. We present our current knowledge of the molecular bases of these critical processes in physiological and pathological conditions, and also highlight open questions that emerge in this expanding field.
    MeSH term(s) Chromatin/genetics ; DNA Repair ; DNA Damage ; Cell Nucleus/genetics ; Signal Transduction
    Chemical Substances Chromatin
    Language English
    Publishing date 2023-06-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2023.102176
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    Zs.A 2963: Show issues Location:
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  2. Article ; Online: Switching genes to silent mode near DNA double-strand breaks.

    Polo, Sophie E

    EMBO reports

    2017  Volume 18, Issue 5, Page(s) 659–660

    MeSH term(s) DNA ; DNA Breaks, Double-Stranded ; DNA Damage ; DNA Repair ; Humans
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2017-03-23
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.201744052
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  3. Article: DNA Double-Strand Break Repair: All Roads Lead to HeterochROMAtin Marks.

    Caron, Pierre / Pobega, Enrico / Polo, Sophie E

    Frontiers in genetics

    2021  Volume 12, Page(s) 730696

    Abstract: In response to DNA double-strand breaks (DSBs), chromatin modifications orchestrate DNA repair pathways thus safeguarding genome integrity. Recent studies have uncovered a key role for heterochromatin marks and associated factors in shaping DSB repair ... ...

    Abstract In response to DNA double-strand breaks (DSBs), chromatin modifications orchestrate DNA repair pathways thus safeguarding genome integrity. Recent studies have uncovered a key role for heterochromatin marks and associated factors in shaping DSB repair within the nucleus. In this review, we present our current knowledge of the interplay between heterochromatin marks and DSB repair. We discuss the impact of heterochromatin features, either pre-existing in heterochromatin domains or
    Language English
    Publishing date 2021-09-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.730696
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  4. Article ; Online: A molecular Rosetta Stone to decipher the impact of chromatin features on the repair of Cas9-mediated DNA double-strand breaks.

    Caron, Pierre / Pobega, Enrico / Polo, Sophie E

    Molecular cell

    2021  Volume 81, Issue 10, Page(s) 2059–2060

    Abstract: Using a barcoded reporter introduced within a thousand different chromatin locations in human cells, (Schep et al., 2021) characterize repair outcomes of Cas9-induced DNA double-strand breaks (DSBs) and the relative use of DSB repair pathways depending ... ...

    Abstract Using a barcoded reporter introduced within a thousand different chromatin locations in human cells, (Schep et al., 2021) characterize repair outcomes of Cas9-induced DNA double-strand breaks (DSBs) and the relative use of DSB repair pathways depending on the local chromatin context.
    MeSH term(s) CRISPR-Cas Systems ; Chromatin/genetics ; DNA ; DNA Breaks, Double-Stranded ; DNA Repair ; Humans
    Chemical Substances Chromatin ; DNA (9007-49-2)
    Language English
    Publishing date 2021-05-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.04.024
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    Zs.A 5055: Show issues Location:
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  5. Article: Imaging the Response to DNA Damage in Heterochromatin Domains.

    Chansard, Audrey / Pobega, Enrico / Caron, Pierre / Polo, Sophie E

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 920267

    Abstract: The eukaryotic genome is assembled in a nucleoprotein complex called chromatin, whose organization markedly influences the repair of DNA lesions. For instance, compact chromatin states, broadly categorized as heterochromatin, present a challenging ... ...

    Abstract The eukaryotic genome is assembled in a nucleoprotein complex called chromatin, whose organization markedly influences the repair of DNA lesions. For instance, compact chromatin states, broadly categorized as heterochromatin, present a challenging environment for DNA damage repair. Through transcriptional silencing, heterochromatin also plays a vital role in the maintenance of genomic integrity and cellular homeostasis. It is thus of critical importance to decipher whether and how heterochromatin affects the DNA damage response (DDR) to understand how this chromatin state is preserved after DNA damage. Here, we present two laser micro-irradiation-based methods for imaging the DDR in heterochromatin domains in mammalian cells. These methods allow DNA damage targeting to specific subnuclear compartments, direct visualization of the DDR and image-based quantification of the repair response. We apply them to study DNA double-strand break repair pathways in facultative heterochromatin and the repair of UV photoproducts in constitutive heterochromatin. We discuss the advantages and limitations of these methods compared to other targeted approaches for DNA damage induction.
    Language English
    Publishing date 2022-06-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.920267
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  6. Article: Mitotic chromatin marking governs asymmetric segregation of DNA damage.

    Ferrand, Juliette / Dabin, Juliette / Chevallier, Odile / Kupai, Ariana / Rothbart, Scott B / Polo, Sophie E

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long- ... ...

    Abstract The faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long-lasting DNA lesions that are segregated during mitosis. How this segregation is controlled is unknown. Here, we uncover a mitotic chromatin-marking pathway that governs the segregation of UV-induced damage in human cells. Our mechanistic analyses reveal two layers of control: histone ADP-ribosylation, and the incorporation of newly synthesized histones at UV damage sites, that both prevent local mitotic phosphorylations on histone H3 serines. Functionally, this chromatin-marking pathway drives the asymmetric segregation of UV damage in the cell progeny with potential consequences on daughter cell fate. We propose that this mechanism may help preserve the integrity of stem cell compartments during asymmetric cell divisions.
    Language English
    Publishing date 2023-09-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.04.556166
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  7. Article: Reshaping Chromatin Architecture around DNA Breaks.

    Caron, Pierre / Polo, Sophie E

    Trends in biochemical sciences

    2019  Volume 45, Issue 3, Page(s) 177–179

    Abstract: DNA double-strand breaks (DSBs) elicit major chromatin changes. Using super-resolution microscopy in human cells, Ochs et al. unveil that the DSB response protein 53BP1 and its effector RIF1 organize DSB-flanking chromatin into circular micro-domains. ... ...

    Abstract DNA double-strand breaks (DSBs) elicit major chromatin changes. Using super-resolution microscopy in human cells, Ochs et al. unveil that the DSB response protein 53BP1 and its effector RIF1 organize DSB-flanking chromatin into circular micro-domains. These structures control the spatial distribution of DSB repair factors safeguarding genome integrity.
    MeSH term(s) Chromatin ; DNA Breaks, Double-Stranded ; DNA Repair ; Humans
    Chemical Substances Chromatin
    Language English
    Publishing date 2019-12-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2019.12.001
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    Zs.A 1207: Show issues Location:
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  8. Article ; Online: Imaging the Response to DNA Damage in Heterochromatin Domains

    Audrey Chansard / Enrico Pobega / Pierre Caron / Sophie E. Polo

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: The eukaryotic genome is assembled in a nucleoprotein complex called chromatin, whose organization markedly influences the repair of DNA lesions. For instance, compact chromatin states, broadly categorized as heterochromatin, present a challenging ... ...

    Abstract The eukaryotic genome is assembled in a nucleoprotein complex called chromatin, whose organization markedly influences the repair of DNA lesions. For instance, compact chromatin states, broadly categorized as heterochromatin, present a challenging environment for DNA damage repair. Through transcriptional silencing, heterochromatin also plays a vital role in the maintenance of genomic integrity and cellular homeostasis. It is thus of critical importance to decipher whether and how heterochromatin affects the DNA damage response (DDR) to understand how this chromatin state is preserved after DNA damage. Here, we present two laser micro-irradiation-based methods for imaging the DDR in heterochromatin domains in mammalian cells. These methods allow DNA damage targeting to specific subnuclear compartments, direct visualization of the DDR and image-based quantification of the repair response. We apply them to study DNA double-strand break repair pathways in facultative heterochromatin and the repair of UV photoproducts in constitutive heterochromatin. We discuss the advantages and limitations of these methods compared to other targeted approaches for DNA damage induction.
    Keywords confocal microscopy ; DNA damage ; DNA repair ; heterochromatin ; laser micro-irradiation ; UV ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Reshaping chromatin after DNA damage: the choreography of histone proteins.

    Polo, Sophie E

    Journal of molecular biology

    2014  Volume 427, Issue 3, Page(s) 626–636

    Abstract: DNA damage signaling and repair machineries operate in a nuclear environment where DNA is wrapped around histone proteins and packaged into chromatin. Understanding how chromatin structure is restored together with the DNA sequence during DNA damage ... ...

    Abstract DNA damage signaling and repair machineries operate in a nuclear environment where DNA is wrapped around histone proteins and packaged into chromatin. Understanding how chromatin structure is restored together with the DNA sequence during DNA damage repair has been a topic of intense research. Indeed, chromatin integrity is central to cell functions and identity. However, chromatin shows remarkable plasticity in response to DNA damage. This review presents our current knowledge of chromatin dynamics in the mammalian cell nucleus in response to DNA double strand breaks and UV lesions. I provide an overview of the key players involved in regulating histone dynamics in damaged chromatin regions, focusing on histone chaperones and their concerted action with histone modifiers, chromatin remodelers and repair factors. I also discuss how these dynamics contribute to reshaping chromatin and, by altering the chromatin landscape, may affect the maintenance of epigenetic information.
    MeSH term(s) Animals ; Chromatin Assembly and Disassembly/genetics ; DNA Damage/genetics ; DNA Repair/genetics ; Histone Chaperones/metabolism ; Histones/metabolism ; Humans
    Chemical Substances Histone Chaperones ; Histones
    Language English
    Publishing date 2014-06-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2014.05.025
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    Zs.A 867: Show issues Location:
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  10. Article ; Online: The response to DNA damage in heterochromatin domains.

    Fortuny, Anna / Polo, Sophie E

    Chromosoma

    2018  Volume 127, Issue 3, Page(s) 291–300

    Abstract: Eukaryotic genomes are organized into chromatin, divided into structurally and functionally distinct euchromatin and heterochromatin compartments. The high level of compaction and the abundance of repeated sequences in heterochromatin pose multiple ... ...

    Abstract Eukaryotic genomes are organized into chromatin, divided into structurally and functionally distinct euchromatin and heterochromatin compartments. The high level of compaction and the abundance of repeated sequences in heterochromatin pose multiple challenges for the maintenance of genome stability. Cells have evolved sophisticated and highly controlled mechanisms to overcome these constraints. Here, we summarize recent findings on how the heterochromatic state influences DNA damage formation, signaling, and repair. By focusing on distinct heterochromatin domains in different eukaryotic species, we highlight the heterochromatin contribution to the compartmentalization of DNA damage repair in the cell nucleus and to the repair pathway choice. We also describe the diverse chromatin alterations associated with the DNA damage response in heterochromatin domains and present our current understanding of their regulatory mechanisms. Finally, we discuss the biological significance and the evolutionary conservation of these processes.
    MeSH term(s) Animals ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; DNA Damage ; DNA Repair ; Heterochromatin/genetics ; Heterochromatin/metabolism ; Histones/metabolism ; Humans ; Signal Transduction
    Chemical Substances Heterochromatin ; Histones
    Language English
    Publishing date 2018-03-29
    Publishing country Austria
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 203083-4
    ISSN 1432-0886 ; 0009-5915
    ISSN (online) 1432-0886
    ISSN 0009-5915
    DOI 10.1007/s00412-018-0669-6
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