Publikation:

Poly(ADP-ribose)-mediated interplay of XPA and PARP1 leads to reciprocal regulation of protein function

Lade...
Vorschaubild

Dateien

Fischer_284916.pdf
Fischer_284916.pdfGröße: 1.52 MBDownloads: 658

Datum

2014

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

DOI (zitierfähiger Link)
ArXiv-ID

Internationale Patentnummer

Angaben zur Forschungsförderung

Projekt

SFB 969 TP B04: Regulation der Proteinfunktion durch Poly(ADP-Ribose)
Open Access-Veröffentlichung
Open Access Hybrid
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

FEBS Journal. 2014, 281(16), pp. 3625-3641. ISSN 1742-464X. eISSN 1742-4658. Available under: doi: 10.1111/febs.12885

Zusammenfassung

Poly(ADP-ribose) (PAR) is a complex and reversible post-translational modification that controls protein function and localization through covalent modification of, or noncovalent binding to target proteins. Previously, we and others characterized the noncovalent, high-affinity binding of the key nucleotide excision repair (NER) protein XPA to PAR. In the present study, we address the functional relevance of this interaction. First, we confirm that pharmacological inhibition of cellular poly(ADP-ribosyl)ation (PARylation) impairs NER efficacy. Second, we demonstrate that the XPA–PAR interaction is mediated by specific basic amino acids within a highly conserved PAR-binding motif, which overlaps the DNA damage-binding protein 2 (DDB2) and transcription factor II H (TFIIH) interaction domains of XPA. Third, biochemical studies reveal a mutual regulation of PARP1 and XPA functions showing that, on the one hand, the XPA–PAR interaction lowers the DNA binding affinity of XPA, whereas, on the other hand, XPA itself strongly stimulates PARP1 enzymatic activity. Fourth, microirradiation experiments in U2OS cells demonstrate that PARP inhibition alters the recruitment properties of XPA-green fluorescent protein to sites of laser-induced DNA damage. In conclusion, our results reveal that XPA and PARP1 regulate each other in a reciprocal and PAR-dependent manner, potentially acting as a fine-tuning mechanism for the spatio-temporal regulation of the two factors during NER.

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 690FISCHER, Jan M.F., Oliver POPP, Daniel GEBHARD, Sebastian VEITH, Arthur FISCHBACH, Sascha BENEKE, Alfred LEITENSTORFER, Jörg BERGEMANN, Martin SCHEFFNER, Elisa FERRANDO-MAY, Aswin MANGERICH, Alexander BÜRKLE, 2014. Poly(ADP-ribose)-mediated interplay of XPA and PARP1 leads to reciprocal regulation of protein function. In: FEBS Journal. 2014, 281(16), pp. 3625-3641. ISSN 1742-464X. eISSN 1742-4658. Available under: doi: 10.1111/febs.12885
BibTex
@article{Fischer2014-08PolyA-28491,
  year={2014},
  doi={10.1111/febs.12885},
  title={Poly(ADP-ribose)-mediated interplay of XPA and PARP1 leads to reciprocal regulation of protein function},
  number={16},
  volume={281},
  issn={1742-464X},
  journal={FEBS Journal},
  pages={3625--3641},
  author={Fischer, Jan M.F. and Popp, Oliver and Gebhard, Daniel and Veith, Sebastian and Fischbach, Arthur and Beneke, Sascha and Leitenstorfer, Alfred and Bergemann, Jörg and Scheffner, Martin and Ferrando-May, Elisa and Mangerich, Aswin and Bürkle, Alexander}
}
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/123456789/28491">
    <dc:contributor>Beneke, Sascha</dc:contributor>
    <dc:contributor>Bergemann, Jörg</dc:contributor>
    <dc:creator>Leitenstorfer, Alfred</dc:creator>
    <dc:contributor>Scheffner, Martin</dc:contributor>
    <dc:creator>Bergemann, Jörg</dc:creator>
    <dc:contributor>Mangerich, Aswin</dc:contributor>
    <dc:contributor>Gebhard, Daniel</dc:contributor>
    <dc:contributor>Fischer, Jan M.F.</dc:contributor>
    <dcterms:bibliographicCitation>FEBS Journal</dcterms:bibliographicCitation>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:title>Poly(ADP-ribose)-mediated interplay of XPA and PARP1 leads to reciprocal regulation of protein function</dcterms:title>
    <dcterms:abstract xml:lang="eng">Poly(ADP-ribose) (PAR) is a complex and reversible post-translational modification that controls protein function and localization through covalent modification of, or noncovalent binding to target proteins. Previously, we and others characterized the noncovalent, high-affinity binding of the key nucleotide excision repair (NER) protein XPA to PAR. In the present study, we address the functional relevance of this interaction. First, we confirm that pharmacological inhibition of cellular poly(ADP-ribosyl)ation (PARylation) impairs NER efficacy. Second, we demonstrate that the XPA–PAR interaction is mediated by specific basic amino acids within a highly conserved PAR-binding motif, which overlaps the DNA damage-binding protein 2 (DDB2) and transcription factor II H (TFIIH) interaction domains of XPA. Third, biochemical studies reveal a mutual regulation of PARP1 and XPA functions showing that, on the one hand, the XPA–PAR interaction lowers the DNA binding affinity of XPA, whereas, on the other hand, XPA itself strongly stimulates PARP1 enzymatic activity. Fourth, microirradiation experiments in U2OS cells demonstrate that PARP inhibition alters the recruitment properties of XPA-green fluorescent protein to sites of laser-induced DNA damage. In conclusion, our results reveal that XPA and PARP1 regulate each other in a reciprocal and PAR-dependent manner, potentially acting as a fine-tuning mechanism for the spatio-temporal regulation of the two factors during NER.</dcterms:abstract>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2014-07-22T08:28:08Z</dc:date>
    <dc:creator>Beneke, Sascha</dc:creator>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/3.0/"/>
    <dc:creator>Bürkle, Alexander</dc:creator>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>Veith, Sebastian</dc:contributor>
    <dc:contributor>Popp, Oliver</dc:contributor>
    <dc:language>eng</dc:language>
    <dc:contributor>Leitenstorfer, Alfred</dc:contributor>
    <dc:creator>Veith, Sebastian</dc:creator>
    <dc:creator>Mangerich, Aswin</dc:creator>
    <dc:creator>Popp, Oliver</dc:creator>
    <dc:creator>Fischer, Jan M.F.</dc:creator>
    <dc:rights>Attribution 3.0 Unported</dc:rights>
    <dc:creator>Fischbach, Arthur</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2014-07-22T08:28:08Z</dcterms:available>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/28491"/>
    <dc:creator>Scheffner, Martin</dc:creator>
    <dc:creator>Gebhard, Daniel</dc:creator>
    <dc:contributor>Ferrando-May, Elisa</dc:contributor>
    <dc:creator>Ferrando-May, Elisa</dc:creator>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/28491/2/Fischer_284916.pdf"/>
    <dc:contributor>Fischbach, Arthur</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/28491/2/Fischer_284916.pdf"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Bürkle, Alexander</dc:contributor>
    <dcterms:issued>2014-08</dcterms:issued>
  </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
Diese Publikation teilen