ATM, KAP1 and the Epstein-Barr virus polymerase processivity factor direct traffic at the intersection of transcription and replication.

Autor:	Xu H; Division of Infectious Diseases, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA., Akinyemi IA; Child Health Research Institute, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA., Haley J; Department of Pathology and Stony Brook Proteomics Center, Stony Brook University, Stony Brook, NY 11794, USA., McIntosh MT; Child Health Research Institute, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA., Bhaduri-McIntosh S; Division of Infectious Diseases, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2023 Nov 10; Vol. 51 (20), pp. 11104-11122.
DOI:	10.1093/nar/gkad823
Abstrakt:	The timing of transcription and replication must be carefully regulated for heavily-transcribed genomes of double-stranded DNA viruses: transcription of immediate early/early genes must decline as replication ramps up from the same genome-ensuring efficient and timely replication of viral genomes followed by their packaging by structural proteins. To understand how the prototypic DNA virus Epstein-Barr 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's 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 and transcription-replication interference pathways orchestrate the handover from transcription-to-replication, a fundamental feature of DNA viruses. (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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