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To understand how the prototypic DNA virus Epstein\u2013Barr virus tackles the logistical challenge of switching from transcription to DNA replication, we examined the proteome at viral replication forks. Specifically, to transition from transcription, the viral DNA polymerase-processivity factor EA-D is SUMOylated by the epigenetic regulator and E3 SUMO-ligase KAP1\/TRIM28. KAP1\u2019s SUMO2-ligase function is triggered by phosphorylation via the PI3K-related kinase ATM and the RNA polymerase II-associated helicase RECQ5 at the transcription machinery. SUMO2-EA-D then recruits the histone loader CAF1 and the methyltransferase SETDB1 to silence the parental genome via H3K9 methylation, prioritizing replication. Thus, a key viral protein and host DNA repair, epigenetic\u00a0and transcription-replication interference pathways orchestrate the handover from transcription-to-replication, a fundamental feature of DNA viruses.<\/jats:p>","DOI":"10.1093\/nar\/gkad823","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T01:18:54Z","timestamp":1697678334000},"page":"11104-11122","source":"Crossref","is-referenced-by-count":14,"title":["ATM, KAP1\u00a0and the Epstein\u2013Barr virus polymerase processivity factor direct traffic at the intersection of transcription and replication"],"prefix":"10.1093","volume":"51","author":[{"given":"Huanzhou","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, University of Florida , Gainesville , FL\u00a0 32610 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibukun A","family":"Akinyemi","sequence":"additional","affiliation":[{"name":"Child Health Research Institute, Department of Pediatrics, University of Florida , Gainesville , FL\u00a0 32610 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Haley","sequence":"additional","affiliation":[{"name":"Department of Pathology and Stony Brook Proteomics Center, Stony Brook University , Stony Brook, NY\u00a0 11794 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5798-3050","authenticated-orcid":false,"given":"Michael T","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Child Health Research Institute, Department of Pediatrics, University of Florida , Gainesville , FL\u00a0 32610 , USA"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida , Gainesville , FL\u00a0 32610 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-9497","authenticated-orcid":false,"given":"Sumita","family":"Bhaduri-McIntosh","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, University of Florida , Gainesville , FL\u00a0 32610 , USA"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida , Gainesville , FL\u00a0 32610 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"2023111117202205000_B1","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1016\/j.cell.2022.08.026","article-title":"Epstein\u2013Barr virus: biology and clinical disease","volume":"185","author":"Damania","year":"2022","journal-title":"Cell"},{"key":"2023111117202205000_B2","doi-asserted-by":"crossref","first-page":"e02247-18","DOI":"10.1128\/JVI.02247-18","article-title":"An epigenetic journey: Epstein-Barr virus transcribes chromatinized and subsequently unchromatinized templates during its lytic cycle","volume":"93","author":"Chakravorty","year":"2019","journal-title":"J. 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