Evidence map›Paper›PMID 19339345›Full record

ArticleJournal of virology2009

Adeno-associated virus replication induces a DNA damage response coordinated by DNA-dependent protein kinase.

Rachel A Schwartz, Christian T Carson, Christine Schuberth, Matthew D Weitzman

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

79 citing papers in PubMed, 111 citations in OpenAlex.

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  19. Nuclear entry and egress of parvoviruses.Molecular microbiology · 2022
    Review
  20. Review

19 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Rachel A SchwartzLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Christian T Carson
Christine Schuberth
Matthew D Weitzman
Salk Institute for Biological Studies · US

Funding

Viral Modulation of Genetic StabilityR01CA097093 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI WEITZMAN, MATTHEW D. · 2003 to 2019
$5.2M
INITIAL STEPS IN RAAV TRANSDUCTIONR01AI043341 · NIAID · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI WEITZMAN, MATTHEW D. · 2000 to 2003
$1.2M
NCI NIH HHS CA97093NCI NIH HHS R01 CA097093NIAID NIH HHS AI43341
6 · The paper itself

Abstract

The parvovirus adeno-associated virus (AAV) contains a small single-stranded DNA genome with inverted terminal repeats that form hairpin structures. In order to propagate, AAV relies on the cellular replication machinery together with functions supplied by coinfecting helper viruses such as adenovirus (Ad). Here, we examined the host cell response to AAV replication in the context of Ad or Ad helper proteins. We show that AAV and Ad coinfection activates a DNA damage response (DDR) that is distinct from that seen during Ad or AAV infection alone. The DDR was also triggered when AAV replicated in the presence of minimal Ad helper proteins. We detected autophosphorylation of the kinases ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and signaling to downstream targets SMC1, Chk1, Chk2, H2AX, and XRCC4 and multiple sites on RPA32. The Mre11 complex was not required for activation of the DDR to AAV infection. Additionally, we found that DNA-PKcs was the primary mediator of damage signaling in response to AAV replication. Immunofluorescence revealed that some activated damage proteins were found in a pan-nuclear pattern (phosphorylated ATM, SMC1, and H2AX), while others such as DNA-PK components (DNA-PKcs, Ku70, and Ku86) and RPA32 accumulated at AAV replication centers. Although expression of the large viral Rep proteins contributed to some damage signaling, we observed that the full response required replication of the AAV genome. Our results demonstrate that AAV replication in the presence of Ad helper functions elicits a unique damage response controlled by DNA-PK.

Indexed as

DNA DamageSignal TransductionVirus ReplicationAdenoviridaeAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsDependovirusDNA-Activated Protein KinaseDNA-Binding ProteinsDNA, ViralHeLa CellsHumansParvoviridae InfectionsPhosphorylationProtein Serine-Threonine KinasesTumor Suppressor ProteinsAtaxia Telangiectasia Mutated ProteinsATM protein, humanCell Cycle ProteinsDNA-Activated Protein KinaseDNA-Binding ProteinsDNA, ViralProtein Serine-Threonine KinasesTumor Suppressor Proteins

Identifiers

PMID19339345
PMCPMC2687378
OpenAlexW2149522560

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.