Epstein-Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S-phase-like cellular environment

Ayumi Kudoh, Masatoshi Fujita, Lumin Zhang, Noriko Shirata, Tohru Daikoku, Yutaka Sugaya, Hiroki Isomura, Yukihiro Nishiyama, Tatsuya Tsurumi

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

When exposed to genotoxic stress, eukaryotic cells demonstrate a DNA damage response with delay or arrest of cell-cycle progression, providing time for DNA repair. Induction of the Epstein-Barr virus (EBV) lytic program elicited a cellular DNA damage response, with activation of the ataxia telangiectasia- mutated (ATM) signal transduction pathway. Activation of the ATM-Rad3-related (ATR) replication checkpoint pathway, in contrast, was minimal. The DNA damage sensor Mre11-Rad50-Nbs1 (MRN) complex and phosphorylated ATM were recruited and retained in viral replication compartments, recognizing newly synthesized viral DNAs as abnormal DNA structures. Phosphorylated p53 also became concentrated in replication compartments and physically interacted with viral BZLF1 protein. Despite the activation of ATM checkpoint signaling, p53-downstream signaling was blocked, with rather high S-phase CDK activity associated with progression of lytic infection. Therefore, although host cells activate ATM checkpoint signaling with response to the lytic viral DNA synthesis, the virus can skillfully evade this host checkpoint security system and actively promote an S-phase-like environment advantageous for viral lytic replication.

Original languageEnglish
Pages (from-to)8156-8163
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number9
DOIs
Publication statusPublished - Mar 4 2005

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Ataxia Telangiectasia
Signal transduction
Virus Replication
Human Herpesvirus 4
S Phase
Viruses
Signal Transduction
DNA Damage
DNA
Chemical activation
Viral DNA
Computer viruses
DNA Viruses
Eukaryotic Cells
Viral Proteins
Cell Cycle Checkpoints
Security systems
DNA Repair
Repair
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Epstein-Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S-phase-like cellular environment. / Kudoh, Ayumi; Fujita, Masatoshi; Zhang, Lumin; Shirata, Noriko; Daikoku, Tohru; Sugaya, Yutaka; Isomura, Hiroki; Nishiyama, Yukihiro; Tsurumi, Tatsuya.

In: Journal of Biological Chemistry, Vol. 280, No. 9, 04.03.2005, p. 8156-8163.

Research output: Contribution to journalArticle

Kudoh, Ayumi ; Fujita, Masatoshi ; Zhang, Lumin ; Shirata, Noriko ; Daikoku, Tohru ; Sugaya, Yutaka ; Isomura, Hiroki ; Nishiyama, Yukihiro ; Tsurumi, Tatsuya. / Epstein-Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S-phase-like cellular environment. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 9. pp. 8156-8163.
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