Viral transport of DNA damage that mimics a stalled replication fork.

Details

Serval ID
serval:BIB_636966E02155
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Viral transport of DNA damage that mimics a stalled replication fork.
Journal
Journal of Virology
Author(s)
Jurvansuu J., Raj K., Stasiak A., Beard P.
ISSN
0022-538X[print], 0022-538X[linking]
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
79
Number
1
Pages
569-580
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Adeno-associated virus type 2 (AAV2) infection incites cells to arrest with 4N DNA content or die if the p53 pathway is defective. This arrest depends on AAV2 DNA, which is single stranded with inverted terminal repeats that serve as primers during viral DNA replication. Here, we show that AAV2 DNA triggers damage signaling that resembles the response to an aberrant cellular DNA replication fork. UV treatment of AAV2 enhances the G2 arrest by generating intrastrand DNA cross-links which persist in infected cells, disrupting viral DNA replication and maintaining the viral DNA in the single-stranded form. In cells, such DNA accumulates into nuclear foci with a signaling apparatus that involves DNA polymerase delta, ATR, TopBP1, RPA, and the Rad9/Rad1/Hus1 complex but not ATM or NBS1. Focus formation and damage signaling strictly depend on ATR and Chk1 functions. Activation of the Chk1 effector kinase leads to the virus-induced G2 arrest. AAV2 provides a novel way to study the cellular response to abnormal DNA replication without damaging cellular DNA. By using the AAV2 system, we show that in human cells activation of phosphorylation of Chk1 depends on TopBP1 and that it is a prerequisite for the appearance of DNA damage foci.
Keywords
Carrier Proteins/metabolism, Cell Line, DNA Damage, DNA Replication, DNA, Viral/biosynthesis, DNA-Binding Proteins, Dependovirus/genetics, Dependovirus/pathogenicity, G2 Phase, Humans, Models, Biological, Nuclear Proteins, Phosphorylation, Protein Kinases/metabolism, Ultraviolet Rays
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 10:36
Last modification date
20/08/2019 14:20
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