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Therefore, many viruses evolved mechanisms to inhibit the DDR network. We have previously shown that the adenovirus (Ad) E4orf4 protein inhibits DDR signaling, but the mechanisms were not identified. Here, we describe an association of E4orf4 with the DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP-1). E4orf4 reduces phosphorylation of this enzyme and inhibits its activity. PARP-1 inhibition assists E4orf4 in reducing Ad-induced DDR signaling and improves the efficiency of virus replication. Furthermore, the ability of E4orf4, when expressed alone, to accumulate at DNA damage sites and to kill cancer cells is attenuated by chemical inhibition of PARP-1. Our results indicate that the E4orf4\u2013PARP-1 interaction has an important role in Ad replication and in promotion of E4orf4-induced cancer-selective cell death.<\/jats:p>","DOI":"10.1128\/jvi.02253-18","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T13:32:53Z","timestamp":1562938373000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["An Interaction with PARP-1 and Inhibition of Parylation Contribute to Attenuation of DNA Damage Signaling by the Adenovirus E4orf4 Protein"],"prefix":"10.1128","volume":"93","author":[{"given":"Keren","family":"Nebenzahl-Sharon","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, 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