PXD060689-1

PXD060689 is an original dataset announced via ProteomeXchange.

Title	Non-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusNon-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusNon-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusV
Description	Vaccinia virus is a large enveloped DNA virus, which, like all poxviruses, replicates in the cytoplasm of infected cells. Vaccinia was historically thought to encode all the proteins required for its replication. However, recent findings have shown that nuclear host proteins are redirected to the cytoplasm to facilitate viral replication. Among these, topoisomerase 2α (TOP2A) and 2β (TOP2B), which mediate nuclear transcription, DNA replication, and chromosome segregation are the most abundant host proteins associated with nascent viral genomes. Here, we investigate the mechanisms driving TOP2A and TOP2B cytoplasmic translocation and their role in viral replication. We found that early viral protein synthesis induces the cytosolic relocalization of both isoforms, which are subsequently recruited to viral factories by an interaction of their C-terminal domains with the viral ligase, A50. TOP2A promotes replication by interacting with the vaccinia DNA replication machinery. In contrast, TOP2B suppresses replication by enhancing the formation of double-stranded RNA and antiviral granules, containing components of the tRNA splicing ligase complex. Our analysis provides new insights into host-pathogen interactions during poxvirus infection and the role of topoisomerase 2 outside of the nucleus.
HostingRepository	PRIDE
AnnounceDate	2025-06-30
AnnouncementXML	Submission_2025-06-29_16:05:38.126.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Skehel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-11 09:44:58	ID requested
⏵ 1	2025-06-29 16:05:39	announced

10.1093/nar/gkaf566;

Dalla Rosa I, Kent L, Way M, in the cytosolic replication of vaccinia virus. Nucleic Acids Res, 53(12):(2025) [pubmed]

submitter keyword: Topoisomerase 2, replication,Vaccinia, lc-ms/ms

Michael Way
contact affiliation	The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. Department of Infectious Disease, Imperial College, London W2 1PG, UK.
contact email	Michael.Way@crick.ac.uk
lab head
Mark Skehel
contact affiliation	Francis Crick Institute
contact email	skehelm@crick.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/06/PXD060689

PRIDE project URI

• PRIDE
  1. PXD060689
     1. Label: PRIDE project
     2. Name: Non-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusNon-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusNon-Redundant Roles of Topoisomerase 2α and 2β in the Cytosolic Replication of Vaccinia VirusV