{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:48:49Z","timestamp":1786992529950,"version":"build-2736575974"},"reference-count":43,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jhep-reports.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JHEP Reports"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.jhepr.2026.101806","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T20:10:37Z","timestamp":1772309437000},"page":"101806","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nucleotide excision repair and poly(ADP-ribose) polymerase 1 cooperate in HBV cccDNA synthesis: A potential viral therapeutic target"],"prefix":"10.1016","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6169-0565","authenticated-orcid":false,"given":"Hsu-Chin","family":"Hung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Wen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-5260","authenticated-orcid":false,"given":"Yung-Tsung","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-6363","authenticated-orcid":false,"given":"Wen-Chun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Hsiung","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8744-6248","authenticated-orcid":false,"given":"Chia-Jui","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ping","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Hsin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsiang","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5049-2475","authenticated-orcid":false,"given":"Hui-Lin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-2678","authenticated-orcid":false,"given":"Ting-Tsung","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-0800","authenticated-orcid":false,"given":"Wenya","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhepr.2026.101806_bib1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A global scientific strategy to cure hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastro Hepat"},{"key":"10.1016\/j.jhepr.2026.101806_bib2","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.3390\/microorganisms9081787","article-title":"Hepatitis B virus DNA integration, chronic infections and hepatocellular carcinoma","volume":"9","author":"Bousali","year":"2021","journal-title":"Microorganisms"},{"key":"10.1016\/j.jhepr.2026.101806_bib3","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.3390\/v13081463","article-title":"Mechanism of hepatitis B virus cccDNA formation","volume":"13","author":"Wei","year":"2021","journal-title":"Viruses"},{"key":"10.1016\/j.jhepr.2026.101806_bib4","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.3390\/cells9112430","article-title":"New insights on molecular mechanism of hepatitis B virus covalently closed circular DNA formation","volume":"9","author":"Marchetti","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.jhepr.2026.101806_bib5","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/s41467-021-21850-9","article-title":"Hepatitis B virus cccDNA is formed through distinct repair processes of each strand","volume":"12","author":"Wei","year":"2021","journal-title":"Nat Comm"},{"key":"10.1016\/j.jhepr.2026.101806_bib6","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007124","article-title":"Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus","volume":"14","author":"Kitamura","year":"2018","journal-title":"Plos Pathog"},{"key":"10.1016\/j.jhepr.2026.101806_bib7","doi-asserted-by":"crossref","first-page":"6220","DOI":"10.3390\/ijms22126220","article-title":"Nucleotide excision repair: from molecular defects to neurological abnormalities","volume":"22","author":"Krasikova","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jhepr.2026.101806_bib8","doi-asserted-by":"crossref","first-page":"11227","DOI":"10.1093\/nar\/gkaa777","article-title":"The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage","volume":"48","author":"Kumar","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jhepr.2026.101806_bib9","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.aohep.2019.12.005","article-title":"Requirement of cyclin-dependent kinase function for hepatitis B virus cccDNA synthesis as measured by digital PCR","volume":"19","author":"Bao","year":"2020","journal-title":"Ann Hepat"},{"key":"10.1016\/j.jhepr.2026.101806_bib10","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/0092-8674(80)90443-2","article-title":"Hepatitis B virus contains protein attached to the 5' terminus of its complete DNA strand","volume":"21","author":"Gerlich","year":"1980","journal-title":"Cell"},{"key":"10.1016\/j.jhepr.2026.101806_bib11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0128401","article-title":"Does tyrosyl DNA phosphodiesterase-2 play a role in hepatitis B virus genome repair?","volume":"10","author":"Cui","year":"2015","journal-title":"PLoS ONE"},{"key":"10.1016\/j.jhepr.2026.101806_bib12","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1093\/nar\/gku088","article-title":"PARP1\u2013TDP1 coupling for the repair of topoisomerase I\u2013induced DNA damage","volume":"42","author":"Das","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jhepr.2026.101806_bib13","first-page":"1856","article-title":"Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication","volume":"8","author":"Ladner","year":"2009","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.jhepr.2026.101806_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-6700-1_1","article-title":"NTCP-reconstituted in vitro HBV infection system","volume":"1540","author":"Sun","year":"2017","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.jhepr.2026.101806_bib15","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.3390\/molecules23123205","article-title":"Function and interactions of ERCC1-XPF in DNA damage response","volume":"23","author":"Faridounnia","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.jhepr.2026.101806_bib16","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01117-18","article-title":"T5 exonuclease hydrolysis of hepatitis B virus replicative intermediates allows reliable quantification and fast drug efficacy testing of covalently closed circular DNA by PCR","volume":"92","author":"Qu","year":"2018","journal-title":"J Virol"},{"key":"10.1016\/j.jhepr.2026.101806_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.100921","article-title":"Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus","volume":"297","author":"Rashid","year":"2021","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jhepr.2026.101806_bib18","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.dnarep.2014.03.020","article-title":"Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2)","volume":"19","author":"Pommier","year":"2014","journal-title":"DNA Repair"},{"key":"10.1016\/j.jhepr.2026.101806_bib19","doi-asserted-by":"crossref","first-page":"12848","DOI":"10.1074\/jbc.M111.333963","article-title":"Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells","volume":"287","author":"Murai","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jhepr.2026.101806_bib20","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.3390\/ijms19072056","article-title":"Effect of TDP2 on the level of TOP2-DNA complexes and SUMOylated TOP2-DNA complexes","volume":"19","author":"Lee","year":"2018","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jhepr.2026.101806_bib21","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/nar\/gkx1219","article-title":"Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation","volume":"46","author":"Kawale","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jhepr.2026.101806_bib22","doi-asserted-by":"crossref","first-page":"E4244","DOI":"10.1073\/pnas.1409986111","article-title":"Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses","volume":"111","author":"K\u00f6Niger","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jhepr.2026.101806_bib23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41467-017-02530-z","article-title":"Structural basis for DNA 3\u2032-end processing by human tyrosyl-DNA phosphodiesterase 1","volume":"9","author":"Flett","year":"2018","journal-title":"Nat Comm"},{"key":"10.1016\/j.jhepr.2026.101806_bib24","doi-asserted-by":"crossref","first-page":"5930","DOI":"10.1093\/emboj\/cdf587","article-title":"The flexible loop of human FEN1 endonuclease is required for flap cleavage during DNA replication and repair","volume":"21","author":"Storici","year":"2002","journal-title":"EMBO J"},{"key":"10.1016\/j.jhepr.2026.101806_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007124","article-title":"Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus","volume":"14","author":"Kitamura","year":"2018","journal-title":"Plos Pathog"},{"key":"10.1016\/j.jhepr.2026.101806_bib26","doi-asserted-by":"crossref","first-page":"21846","DOI":"10.1074\/jbc.M111.337899","article-title":"Multiple DNA binding domains mediate the function of the ERCC1-XPF protein in nucleotide excision repair","volume":"287","author":"Su","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jhepr.2026.101806_bib27","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/j.str.2005.08.014","article-title":"The structure of the human ERCC1\/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair","volume":"13","author":"Tripsianes","year":"2005","journal-title":"Structure"},{"key":"10.1016\/j.jhepr.2026.101806_bib28","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1093\/emboj\/21.8.2045","article-title":"The active site of the DNA repair endonuclease XPF-ERCC1 forms a highly conserved nuclease motif","volume":"21","author":"Enzlin","year":"2002","journal-title":"EMBO J"},{"key":"10.1016\/j.jhepr.2026.101806_bib29","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1074\/jbc.M116.747857","article-title":"Single-stranded DNA binding by the helix-hairpin-helix domain of XPF protein contributes to the substrate specificity of the ERCC1-XPF protein complex","volume":"292","author":"Das","year":"2017","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jhepr.2026.101806_bib30","doi-asserted-by":"crossref","first-page":"747","DOI":"10.2217\/fon.14.313","article-title":"Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer","volume":"11","author":"Gunderson","year":"2015","journal-title":"Fut Oncol"},{"issue":"1","key":"10.1016\/j.jhepr.2026.101806_bib31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13073-024-01370-z","article-title":"The PARP1 selective inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in patient-derived BRCA1\/2-associated cancer models","volume":"16","author":"Herencia-Ropero","year":"2024","journal-title":"Genome Med"},{"issue":"3","key":"10.1016\/j.jhepr.2026.101806_bib32","doi-asserted-by":"crossref","first-page":"370","DOI":"10.21147\/j.issn.1000-9604.2020.03.08","article-title":"Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors","volume":"32","author":"Li","year":"2020","journal-title":"Chin J Cancer Res"},{"key":"10.1016\/j.jhepr.2026.101806_bib33","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1136\/gutjnl-2022-328380","article-title":"Quantification of the hepatitis B virus cccDNA: evidence-based guidelines for monitoring the key obstacle of HBV cure","volume":"72","author":"Allweiss","year":"2023","journal-title":"Gut"},{"key":"10.1016\/j.jhepr.2026.101806_bib34","doi-asserted-by":"crossref","first-page":"11236","DOI":"10.1073\/pnas.0504341102","article-title":"Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1","volume":"102","author":"Tsodikov","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jhepr.2026.101806_bib35","doi-asserted-by":"crossref","first-page":"36518","DOI":"10.1074\/jbc.M508898200","article-title":"Human Tdp1 cleaves a broad spectrum of substrates including phosphoamide linkages","volume":"280","author":"Interthal","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jhepr.2026.101806_bib36","article-title":"Host 3' flap endonuclease Mus81 plays a critical role in trimming the terminal redundancy of hepatitis B virus relaxed circular DNA during covalently closed circular DNA formation","volume":"21","author":"Zhang","year":"2025","journal-title":"Plos Pathog"},{"key":"10.1016\/j.jhepr.2026.101806_bib37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41564-020-0678-0","article-title":"Core components of DNA lagging strand synthesis machinery are essential for hepatitis B virus cccDNA formation","volume":"5","author":"Wei","year":"2020","journal-title":"Nat Microbiol"},{"key":"10.1016\/j.jhepr.2026.101806_bib38","doi-asserted-by":"crossref","first-page":"9908","DOI":"10.1021\/acs.jmedchem.8b00639","article-title":"Discovery, synthesis, and evaluation of oxynitidine derivatives as dual inhibitors of DNA topoisomerase IB (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1), and potential antitumor agents","volume":"61","author":"Zhang","year":"2018","journal-title":"J Med Chem"},{"key":"10.1016\/j.jhepr.2026.101806_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2020.564601","article-title":"PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance","volume":"8","author":"Rose","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.jhepr.2026.101806_bib40","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.gpb.2016.05.001","article-title":"Functions of PARylation in DNA damage repair pathways","volume":"14","author":"Wei","year":"2016","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"10.1016\/j.jhepr.2026.101806_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2022.1073797","article-title":"The potential of PARP inhibitors in targeted cancer therapy and immunotherapy","volume":"9","author":"Hunia","year":"2022","journal-title":"Front Mol Biosci"},{"key":"10.1016\/j.jhepr.2026.101806_bib42","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.00585-22","article-title":"DNA repair factor Poly(ADP-Ribose) polymerase 1 is a proviral factor in hepatitis B virus covalently closed circular DNA formation","volume":"96","author":"Chen","year":"2022","journal-title":"J Virol"},{"key":"10.1016\/j.jhepr.2026.101806_bib43","article-title":"Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma","volume":"7","author":"Zhao","year":"2016","journal-title":"Nat Commun"}],"container-title":["JHEP Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555926000777?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555926000777?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:25:21Z","timestamp":1783632321000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589555926000777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["S2589555926000777"],"URL":"https:\/\/doi.org\/10.1016\/j.jhepr.2026.101806","relation":{},"ISSN":["2589-5559"],"issn-type":[{"value":"2589-5559","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nucleotide excision repair and poly(ADP-ribose) polymerase 1 cooperate in HBV cccDNA synthesis: A potential viral therapeutic target","name":"articletitle","label":"Article Title"},{"value":"JHEP Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhepr.2026.101806","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).","name":"copyright","label":"Copyright"}],"article-number":"101806"}}