Evidence map›Paper›PMID 21188139›Full record

ArticlePloS one2010

The effect of DNA-dependent protein kinase on adeno-associated virus replication.

Young-Kook Choi, Kevin Nash, Barry J Byrne, Nicholas Muzyczka, Sihong Song

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  7. Transcriptional Responses ofJournal of fungi (Basel, Switzerland) · 2021
    Article
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  16. Parvovirus diversity and DNA damage responses.Cold Spring Harbor perspectives in biology · 2013
    Review
  17. Article
  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

5 authors at 1 institution in 1 country.

Young-Kook ChoiDepartment of Pharmaceutics, University of Florida, Gainesville, Florida, United States of America.
Kevin Nash
Barry J Byrne
Nicholas Muzyczka
Sihong Song
University of Florida · US

Funding

VIRAL VECTOR DELIVERY OF ANTISENSE TO ACE MRNA IN CARDIOVASCULAR DISEASEP01HL059412 · NHLBI · UNIVERSITY OF FLORIDA · PI MUZYCZKA, NICHOLAS · 1998 to 2012
$20.2M
Vector CoreP01HL051811 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI GUGGINO, WILLIAM B. · 1993 to 2013
$20.2M
Strategies for Sustained Effect of AAV-mediated Correction of Pompe DiseaseP01DK058327 · NIDDK · UNIVERSITY OF FLORIDA · PI CAMPBELL-THOMPSON, MARTHA · 2000 to 2009
$11.0M
NHLBI NIH HHS P01 HL051811NHLBI NIH HHS P01 HL059412NHLBI NIH HHS P01 HL51811NHLBI NIH HHS P01 HL59412NIDDK NIH HHS P01 DK058327NIDDK NIH HHS P01-DK58327
6 · The paper itself

Abstract

backgroundDNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and plays an important role in determining the molecular fate of the rAAV genome. However, the effect this cellular enzyme on rAAV DNA replication remains elusive. METHODOLOGY/PRINCIPAL

findingsIn the present study, we characterized the roles of DNA-PK on recombinant adeno-associated virus DNA replication. Inhibition of DNA-PK by a DNA-PK inhibitor or siRNA targeting DNA-PKcs significantly decreased replication of AAV in MO59K and 293 cells. Southern blot analysis showed that replicated rAAV DNA formed head-to-head or tail-to-tail junctions. The head-to-tail junction was low or undetectable suggesting AAV-ITR self-priming is the major mechanism for rAAV DNA replication. In an in vitro replication assay, anti-Ku80 antibody strongly inhibited rAAV replication, while anti-Ku70 antibody moderately decreased rAAV replication. Similarly, when Ku heterodimer (Ku70/80) was depleted, less replicated rAAV DNA were detected. Finally, we showed that AAV-ITRs directly interacted with Ku proteins. CONCLUSION/SIGNIFICANCE: Collectively, our results showed that that DNA-PK enhances rAAV replication through the interaction of Ku proteins and AAV-ITRs.

Indexed as

Virus ReplicationAndrostadienesAntigens, NuclearBlotting, SouthernCell LineCell Line, TumorDependovirusDimerizationDNA-Activated Protein KinaseDNA-Binding ProteinsDNA ReplicationEnzyme InhibitorsGenome, ViralHumansKu AutoantigenRNA, Small InterferingAndrostadienesAntigens, NuclearDNA-Activated Protein KinaseDNA-Binding ProteinsEnzyme InhibitorsKu AutoantigenRNA, Small InterferingWortmanninXrcc6 protein, human

Identifiers

PMID21188139
PMCPMC3004791
OpenAlexW2023491408

What OpenQuestion holds

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LicenceCC BY
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.