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Differential and Concordant Roles for Poly(ADP-Ribose) Polymerase 1 and poly(ADP-Ribose) in Regulating WRN and RECQL5 Activities

Differential and Concordant Roles for Poly(ADP-Ribose) Polymerase 1 and poly(ADP-Ribose) in Regulating WRN and RECQL5 Activities

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KHADKA, Prabhat, Joseph K. HSU, Sebastian VEITH, Takashi TADOKORO, Raghavendra SHAMANNA, Aswin MANGERICH, Deborah L. CROTEAU, Vilhelm A. BOHR, 2015. Differential and Concordant Roles for Poly(ADP-Ribose) Polymerase 1 and poly(ADP-Ribose) in Regulating WRN and RECQL5 Activities. In: Molecular and Cellular Biology. 35(23), pp. 3974-3989. ISSN 0270-7306. eISSN 1098-5549

@article{Khadka2015-12-01Diffe-31846, title={Differential and Concordant Roles for Poly(ADP-Ribose) Polymerase 1 and poly(ADP-Ribose) in Regulating WRN and RECQL5 Activities}, year={2015}, doi={10.1128/MCB.00427-15}, number={23}, volume={35}, issn={0270-7306}, journal={Molecular and Cellular Biology}, pages={3974--3989}, author={Khadka, Prabhat and Hsu, Joseph K. and Veith, Sebastian and Tadokoro, Takashi and Shamanna, Raghavendra and Mangerich, Aswin and Croteau, Deborah L. and Bohr, Vilhelm A.} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/31846"> <dc:creator>Khadka, Prabhat</dc:creator> <dc:creator>Bohr, Vilhelm A.</dc:creator> <dc:contributor>Veith, Sebastian</dc:contributor> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/31846"/> <dc:contributor>Hsu, Joseph K.</dc:contributor> <dc:creator>Tadokoro, Takashi</dc:creator> <dc:language>eng</dc:language> <dc:creator>Mangerich, Aswin</dc:creator> <dcterms:abstract xml:lang="eng">Poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the polyADP(ribosyl)ation (PARylation) of proteins, a post-translational modification which forms the nucleic acid-like polymer poly(ADP-ribose) (PAR). PARP1 and PAR are integral players in the early DNA damage response, since PARylation orchestrates the recruitment of repair proteins to the damage sites. Human RecQ helicases are DNA unwinding proteins that are critical responders to DNA damage, but how their recruitment and activities are regulated by PARPs and PAR is poorly understood. Here we report that all human RecQ helicases interact with PAR non-covalently. Furthermore, we define the effects that PARP1, PARylated PARP1 and PAR have on RECQL5 and WRN, using both in vitro and in vivo assays. We show that PARylation is involved in the recruitment of RECQL5 and WRN to laser-induced DNA damage and that RECQL5 and WRN have a differential response to PARylated PARP1 and PAR. Furthermore, we show that RECQL5 or WRN loss resulted in increased sensitivity towards PARP inhibition. In conclusion, our results demonstrate that PARP1 and PAR actively, and in some instances differentially, regulate the activities and cellular localization of RECQL5 and WRN, suggesting that PARylation acts as a fine-tuning mechanism to coordinate their functions in time and space during genotoxic stress response.</dcterms:abstract> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-09-28T09:30:28Z</dcterms:available> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-09-28T09:30:28Z</dc:date> <dc:contributor>Bohr, Vilhelm A.</dc:contributor> <dcterms:issued>2015-12-01</dcterms:issued> <dc:contributor>Khadka, Prabhat</dc:contributor> <dc:contributor>Shamanna, Raghavendra</dc:contributor> <dc:creator>Veith, Sebastian</dc:creator> <dc:creator>Croteau, Deborah L.</dc:creator> <dc:creator>Shamanna, Raghavendra</dc:creator> <dc:contributor>Croteau, Deborah L.</dc:contributor> <dc:contributor>Tadokoro, Takashi</dc:contributor> <dcterms:title>Differential and Concordant Roles for Poly(ADP-Ribose) Polymerase 1 and poly(ADP-Ribose) in Regulating WRN and RECQL5 Activities</dcterms:title> <dc:contributor>Mangerich, Aswin</dc:contributor> <dc:creator>Hsu, Joseph K.</dc:creator> </rdf:Description> </rdf:RDF>

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