Evidence map›Paper›PMID 22072974›Full record

ArticlePLoS pathogens2011

Single molecule analysis of replicated DNA reveals the usage of multiple KSHV genome regions for latent replication.

Subhash C Verma, Jie Lu, Qiliang Cai, Settapong Kosiyatrakul, Maria E McDowell, Carl L Schildkraut, Erle S Robertson

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

25 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
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  14. Article
  15. KSHV Genome Replication and Maintenance.Frontiers in microbiology · 2016
    Review
  16. The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  17. Review
  18. Article
  19. Article
  20. Review
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

7 authors at 3 institutions in 1 country.

Subhash C VermaDepartment of Microbiology & Immunology, University of Nevada, Reno, Nevada, United States of America. scverma@medicine.nevada.edu
Jie Lu
Qiliang Cai
Settapong Kosiyatrakul
Maria E McDowell
Carl L Schildkraut
Erle S Robertson
University of Pennsylvania · USAlbert Einstein College of Medicine · USUniversity of Nevada, Reno · US

Funding

DNA REPLICATION INITIATION SITES IN MAMMALIAN CELLSR01GM045751 · NIGMS · YESHIVA UNIVERSITY · PI SCHILDKRAUT, CARL L · 1992 to 2023
$13.4M
Mechanisms of Action of LANA encoded by KSHVR01CA091792 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2002 to 2011
$3.4M
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 CA072510NCI NIH HHS CA 091792NCI NIH HHS CA126182NCI NIH HHS K99 CA126182NCI NIH HHS R00 CA126182NCI NIH HHS R01 CA091792NIGMS NIH HHS GM045751NIGMS NIH HHS R01 GM045751
6 · The paper itself

Abstract

Kaposi's sarcoma associated herpesvirus (KSHV), an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA). Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD). Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR) plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA sequences.

Indexed as

Genome, ViralVirus ReplicationAntigens, ViralCell CycleCell Cycle ProteinsCell Line, TumorChromatin ImmunoprecipitationDNA-Binding ProteinsDNA ReplicationDNA, ViralHerpesvirus 8, HumanHumansMinichromosome Maintenance Complex Component 3Nuclear ProteinsOrigin Recognition ComplexReplication OriginAntigens, ViralCell Cycle ProteinsDNA-Binding ProteinsDNA, Virallatency-associated nuclear antigenMCM3 protein, humanMinichromosome Maintenance Complex Component 3Nuclear ProteinsORC2 protein, humanOrigin Recognition Complex

Identifiers

PMID22072974
PMCPMC3207954
OpenAlexW2066192691

What OpenQuestion holds

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LicenceCC BY
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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.