Restriction of AID activity and somatic hypermutation by PARP-1

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

@article{Tepper2019-08-22Restr-46006, title={Restriction of AID activity and somatic hypermutation by PARP-1}, year={2019}, doi={10.1093/nar/gkz466}, 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 xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dc:contributor>Członka, Ewelina</dc:contributor> <dcterms:hasPart rdf:resource=""/> <dc:date rdf:datatype="">2019-06-13T12:54:41Z</dc:date> <dc:contributor>Mangerich, Aswin</dc:contributor> <bibo:uri rdf:resource=""/> <dc:creator>Jungnickel, Berit</dc:creator> <dc:contributor>Mortusewicz, Oliver</dc:contributor> <dcterms:issued>2019-08-22</dcterms:issued> <dspace:isPartOfCollection rdf:resource=""/> <dc:contributor>Tepper, Sandra</dc:contributor> <dc:creator>Jeschke, Julia</dc:creator> <dc:contributor>Fischbach, Arthur</dc:contributor> <dc:contributor>Pfeil, Ines</dc:contributor> <dc:language>eng</dc:language> <dcterms:isPartOf rdf:resource=""/> <dc:creator>Mangerich, Aswin</dc:creator> <dc:creator>Pfeil, Ines</dc:creator> <dc:contributor>Jungnickel, Berit</dc:contributor> <dc:contributor>Bello, Amanda</dc:contributor> <dcterms:rights rdf:resource=""/> <dc:contributor>Jeschke, Julia</dc:contributor> <dc:creator>Fischbach, Arthur</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>Bello, Amanda</dc:creator> <dc:rights>Attribution 4.0 International</dc:rights> <dspace:hasBitstream rdf:resource=""/> <dc:creator>Tepper, Sandra</dc:creator> <dc:creator>Schmidt, Angelika</dc:creator> <dcterms:available rdf:datatype="">2019-06-13T12:54:41Z</dcterms:available> <dc:creator>Członka, Ewelina</dc:creator> <dc:creator>Mortusewicz, Oliver</dc:creator> <dcterms:title>Restriction of AID activity and somatic hypermutation by PARP-1</dcterms:title> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Schmidt, Angelika</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> </rdf:Description> </rdf:RDF>

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