Publikation:

Restriction of AID activity and somatic hypermutation by PARP-1

Vorschaubild

Dateien

Tepper_2-qflcz6didc1u6.pdf
Tepper_2-qflcz6didc1u6.pdfGröße: 4.27 MBDownloads: 241

Datum

2019

Autor:innen

Tepper, Sandra
Mortusewicz, Oliver
Członka, Ewelina
Bello, Amanda
Schmidt, Angelika
Jeschke, Julia
Pfeil, Ines
Jungnickel, Berit
et al.

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

URI (zitierfähiger Link)
http://nbn-resolving.de/urn:nbn:de:bsz:352-2-qflcz6didc1u6
DOI (zitierfähiger Link)
https://doi.org/10.1093/nar/gkz466
ArXiv-ID

Internationale Patentnummer

Link zur Lizenz

CC BY 4.0

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Gold

Sammlungen

Biologie: Publikationen
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Nucleic Acids Research. 2019, 47(14), pp. 7418-7429. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gkz466

Zusammenfassung

Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has been identified to date. Here we show that poly(ADP-ribose) polymerase-1 (PARP-1) is a key factor restricting AID activity during somatic hypermutation. Poly(ADP-ribose) (PAR) chains formed at DNA breaks trigger AID-PAR association, thus preventing excessive DNA damage induction at sites of AID action. Accordingly, AID activity and somatic hypermutation at the Ig variable region is decreased by PARP-1 activity. In addition, PARP-1 regulates DNA lesion processing by affecting strand biased A:T mutagenesis. Our study establishes a novel function of the ancestral genome maintenance factor PARP-1 as a critical local feedback regulator of both AID activity and DNA repair during Ig gene diversification.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690TEPPER, Sandra, Oliver MORTUSEWICZ, Ewelina CZŁONKA, Amanda BELLO, Angelika SCHMIDT, Julia JESCHKE, Arthur FISCHBACH, Ines PFEIL, Aswin MANGERICH, Berit JUNGNICKEL, 2019. Restriction of AID activity and somatic hypermutation by PARP-1. In: Nucleic Acids Research. 2019, 47(14), pp. 7418-7429. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gkz466
BibTex
@article{Tepper2019-08-22Restr-46006,
  year={2019},
  doi={10.1093/nar/gkz466},
  title={Restriction of AID activity and somatic hypermutation by PARP-1},
  number={14},
  volume={47},
  issn={0305-1048},
  journal={Nucleic Acids Research},
  pages={7418--7429},
  author={Tepper, Sandra and Mortusewicz, Oliver and Członka, Ewelina and Bello, Amanda and Schmidt, Angelika and Jeschke, Julia and Fischbach, Arthur and Pfeil, Ines and Mangerich, Aswin and Jungnickel, Berit}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/46006">
    <dc:contributor>Pfeil, Ines</dc:contributor>
    <dc:creator>Jeschke, Julia</dc:creator>
    <dc:contributor>Jeschke, Julia</dc:contributor>
    <dc:creator>Bello, Amanda</dc:creator>
    <dc:contributor>Mortusewicz, Oliver</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:creator>Mortusewicz, Oliver</dc:creator>
    <dc:contributor>Schmidt, Angelika</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-06-13T12:54:41Z</dc:date>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/46006"/>
    <dc:contributor>Jungnickel, Berit</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/46006/1/Tepper_2-qflcz6didc1u6.pdf"/>
    <dc:contributor>Fischbach, Arthur</dc:contributor>
    <dc:contributor>Mangerich, Aswin</dc:contributor>
    <dcterms:abstract xml:lang="eng">Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has been identified to date. Here we show that poly(ADP-ribose) polymerase-1 (PARP-1) is a key factor restricting AID activity during somatic hypermutation. Poly(ADP-ribose) (PAR) chains formed at DNA breaks trigger AID-PAR association, thus preventing excessive DNA damage induction at sites of AID action. Accordingly, AID activity and somatic hypermutation at the Ig variable region is decreased by PARP-1 activity. In addition, PARP-1 regulates DNA lesion processing by affecting strand biased A:T mutagenesis. Our study establishes a novel function of the ancestral genome maintenance factor PARP-1 as a critical local feedback regulator of both AID activity and DNA repair during Ig gene diversification.</dcterms:abstract>
    <dcterms:issued>2019-08-22</dcterms:issued>
    <dc:creator>Mangerich, Aswin</dc:creator>
    <dc:creator>Fischbach, Arthur</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-06-13T12:54:41Z</dcterms:available>
    <dc:contributor>Członka, Ewelina</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/46006/1/Tepper_2-qflcz6didc1u6.pdf"/>
    <dc:creator>Schmidt, Angelika</dc:creator>
    <dc:creator>Tepper, Sandra</dc:creator>
    <dcterms:title>Restriction of AID activity and somatic hypermutation by PARP-1</dcterms:title>
    <dc:creator>Pfeil, Ines</dc:creator>
    <dc:contributor>Tepper, Sandra</dc:contributor>
    <dc:creator>Jungnickel, Berit</dc:creator>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Członka, Ewelina</dc:creator>
    <dc:language>eng</dc:language>
    <dc:contributor>Bello, Amanda</dc:contributor>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen