Evidence map›Paper›PMID 22761383›Full record

ArticleJournal of virology2012

Kaposi's sarcoma-associated herpesvirus-encoded LANA recruits topoisomerase IIβ for latent DNA replication of the terminal repeats.

Pravinkumar Purushothaman, Maria E McDowell, James McGuinness, Ruth Salas, Sharif M Rumjahn, Subhash C Verma

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. KSHV Genome Replication and Maintenance.Frontiers in microbiology · 2016
    Review
  11. Kaposi's Sarcoma Herpesvirus Genome Persistence.Frontiers in microbiology · 2016
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Pravinkumar PurushothamanDepartment of Microbiology & Immunology, University of Nevada, Reno, School of Medicine, Center for Molecular Medicine, Reno, Nevada, USA.
Maria E McDowell
James McGuinness
Ruth Salas
Sharif M Rumjahn
Subhash C Verma
University of Nevada, Reno · US

Funding

Understanding the mechanism of KSHV latent DNA replicationR00CA126182 · NCI · UNIVERSITY OF NEVADA RENO · PI VERMA, SUBHASH C · 2009 to 2011
$740k
Understanding the mechanism of KSHV latent DNA replicationK99CA126182 · NCI · UNIVERSITY OF PENNSYLVANIA · PI VERMA, SUBHASH C · 2007 to 2008
$250k
NCI NIH HHS CA126182NCI NIH HHS K99 CA126182NCI NIH HHS R00 CA126182
6 · The paper itself

Abstract

The latency-associated nuclear antigen (LANA) encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) plays a major role in maintaining latency and is critical for the perpetual segregation of viral episomes to the progeny nuclei of newly divided cells. LANA binds to KSHV terminal repeat (TR) DNA and tethers the viral episomes to host chromosomes through the association of chromatin-bound cellular proteins. TR elements serve as potential origin sites of KSHV replication and have been shown to play important roles in latent DNA replication and transcription of adjacent genes. Affinity chromatography and proteomics analysis using KSHV TR DNA and the LANA binding site as the affinity column identified topoisomerase IIβ (TopoIIβ) as a LANA-interacting protein. Here, we show that TopoIIβ forms complexes with LANA that colocalize as punctuate bodies in the nucleus of KSHV-infected cells. The specific TopoIIβ binding region of LANA has been identified to its N terminus and the first 32 amino acid residues containing the nucleosome-binding region crucial for binding. Moreover, this region could also act as a dominant negative to disrupt association of TopoIIβ with LANA. TopoIIβ plays an important role in LANA-dependent latent DNA replication, as addition of ellipticine, a selective inhibitor of TopoII, negatively regulated replication mediated by the TR. DNA break labeling and chromatin immunoprecipitation assay using biotin-16-dUTP and terminal deoxynucleotide transferase showed that TopoIIβ mediates a transient DNA break on viral DNA. These studies confirm that LANA recruits TopoIIβ at the origins of latent replication to unwind the DNA for replication.

Indexed as

DNA ReplicationAmino Acid SequenceAnimalsAntigens, ViralBase SequenceCell LineCell NucleusDNA-Binding ProteinsDNA Topoisomerases, Type IIDNA, ViralEllipticinesHEK293 CellsHerpesvirus 8, HumanHost-Pathogen InteractionsHumansMiceAntigens, ViralDNA-Binding ProteinsDNA Topoisomerases, Type IIDNA, ViralellipticineEllipticineslatency-associated nuclear antigenNuclear ProteinsTopoisomerase II Inhibitors

Identifiers

PMID22761383
PMCPMC3446556
OpenAlexW2162975410

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.