{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:55:23Z","timestamp":1793087723324,"version":"4.5.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,4]]},"abstract":"<jats:p>A previously described mammalian cell activity, called VPg unlinkase, specifically cleaves a unique protein\u2013RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection. For over three decades, the identity of this cellular activity and its normal role in the uninfected cell had remained elusive. Here we report the purification and identification of VPg unlinkase as the DNA repair enzyme, 5\u2032-tyrosyl\u2013DNA phosphodiesterase-2 (TDP2). Our data show that VPg unlinkase activity in different mammalian cell lines correlates with their differential expression of TDP2. Furthermore, we show that recombinant TDP2 can cleave the protein\u2013RNA linkage generated by different picornaviruses without impairing the integrity of viral RNA. Our results reveal a unique RNA repair-like function for TDP2 and suggest an unusual role in host\u2013pathogen interactions for this cellular enzyme. On the basis of the identification of TDP2 as a potential antiviral target, our findings may lead to the development of universal therapeutics to treat the millions of individuals afflicted annually with diseases caused by picornaviruses, including myocarditis, aseptic meningitis, encephalitis, hepatitis, and the common cold.<\/jats:p>","DOI":"10.1073\/pnas.1208096109","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T00:30:12Z","timestamp":1345509012000},"page":"14634-14639","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":87,"title":["An RNA virus hijacks an incognito function of a DNA repair enzyme"],"prefix":"10.1073","volume":"109","author":[{"given":"Richard","family":"Virgen-Slane","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet M.","family":"Rozovics","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry D.","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Ngo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerbrand J.","family":"van der Heden van Noort","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri V.","family":"Filippov","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Gershon","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert L.","family":"Semler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,20]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"107","volume-title":"The Picornaviruses","author":"Rozovics JM","year":"2010","unstructured":"JM Rozovics, BL Semler, Genome replication I: the players. 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