HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 9, 8156-8163, March 4, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/9/8156    most recent M411405200v2 M411405200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kudoh, A. Articles by Tsurumi, T. Search for Related Content PubMed PubMed Citation Articles by Kudoh, A. Articles by Tsurumi, T. Social Bookmarking                      What's this?

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, and Tatsuya Tsurumi**

From the Division of Virology, Aichi Cancer Center Research Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan, the ^||Virology Division, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan, and the Department of Virology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan

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.

Received for publication, October 6, 2004 , and in revised form, December 15, 2004.

^* This work was supported by Grants-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan (16017322 and 15390153, to T. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

^** To whom correspondence should be addressed: Division of Virology, Aichi Cancer Center Research Institute, 1-1, Kanokoden, Chikusaku, Nagoya 464-8681, Japan. Tel./Fax: 81-52-764-2979; E-mail: ttsurumi{at}aichi-cc.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Iwahori, T. Murata, A. Kudoh, Y. Sato, S. Nakayama, H. Isomura, T. Kanda, and T. Tsurumi Phosphorylation of p27Kip1 by Epstein-Barr Virus Protein Kinase Induces Its Degradation through SCFSkp2 Ubiquitin Ligase Actions during Viral Lytic Replication J. Biol. Chem., July 10, 2009; 284(28): 18923 - 18931. [Abstract] [Full Text] [PDF]

				A. Kudoh, S. Iwahori, Y. Sato, S. Nakayama, H. Isomura, T. Murata, and T. Tsurumi Homologous Recombinational Repair Factors Are Recruited and Loaded onto the Viral DNA Genome in Epstein-Barr Virus Replication Compartments J. Virol., July 1, 2009; 83(13): 6641 - 6651. [Abstract] [Full Text] [PDF]

				G. J. Nichols, J. Schaack, and D. A. Ornelles Widespread Phosphorylation of Histone H2AX by Species C Adenovirus Infection Requires Viral DNA Replication J. Virol., June 15, 2009; 83(12): 5987 - 5998. [Abstract] [Full Text] [PDF]

				R. A. Schwartz, C. T. Carson, C. Schuberth, and M. D. Weitzman Adeno-Associated Virus Replication Induces a DNA Damage Response Coordinated by DNA-Dependent Protein Kinase J. Virol., June 15, 2009; 83(12): 6269 - 6278. [Abstract] [Full Text] [PDF]

				T. Murata, Y. Sato, S. Nakayama, A. Kudoh, S. Iwahori, H. Isomura, M. Tajima, T. Hishiki, T. Ohshima, M. Hijikata, et al. TORC2, a Coactivator of cAMP-response Element-binding Protein, Promotes Epstein-Barr Virus Reactivation from Latency through Interaction with Viral BZLF1 Protein J. Biol. Chem., March 20, 2009; 284(12): 8033 - 8041. [Abstract] [Full Text] [PDF]

				J. C. Forrest and S. H. Speck Establishment of B-Cell Lines Latently Infected with Reactivation-Competent Murine Gammaherpesvirus 68 Provides Evidence for Viral Alteration of a DNA Damage-Signaling Cascade J. Virol., August 1, 2008; 82(15): 7688 - 7699. [Abstract] [Full Text] [PDF]

				B. Oster, B. Bundgaard, T. R. Hupp, and P. Hollsberg Human herpesvirus 6B induces phosphorylation of p53 in its regulatory domain by a CK2- and p38-independent pathway J. Gen. Virol., January 1, 2008; 89(1): 87 - 96. [Abstract] [Full Text] [PDF]

				C.-C. Lu, Y.-C. Chen, J.-T. Wang, P.-W. Yang, and M.-R. Chen Xeroderma pigmentosum C is involved in Epstein Barr virus DNA replication J. Gen. Virol., December 1, 2007; 88(12): 3234 - 3243. [Abstract] [Full Text] [PDF]

				S. Iwahori, N. Shirata, Y. Kawaguchi, S. K. Weller, Y. Sato, A. Kudoh, S. Nakayama, H. Isomura, and T. Tsurumi Enhanced Phosphorylation of Transcription Factor Sp1 in Response to Herpes Simplex Virus Type 1 Infection Is Dependent on the Ataxia Telangiectasia-Mutated Protein J. Virol., September 15, 2007; 81(18): 9653 - 9664. [Abstract] [Full Text] [PDF]

				C.-P. Lee, J.-Y. Chen, J.-T. Wang, K. Kimura, A. Takemoto, C.-C. Lu, and M.-R. Chen Epstein-Barr Virus BGLF4 Kinase Induces Premature Chromosome Condensation through Activation of Condensin and Topoisomerase II J. Virol., May 15, 2007; 81(10): 5166 - 5180. [Abstract] [Full Text] [PDF]

				M. H. Luo, K. Rosenke, K. Czornak, and E. A. Fortunato Human Cytomegalovirus Disrupts both Ataxia Telangiectasia Mutated Protein (ATM)- and ATM-Rad3-Related Kinase-Mediated DNA Damage Responses during Lytic Infection J. Virol., February 15, 2007; 81(4): 1934 - 1950. [Abstract] [Full Text] [PDF]

				A. Kudoh, T. Daikoku, Y. Ishimi, Y. Kawaguchi, N. Shirata, S. Iwahori, H. Isomura, and T. Tsurumi Phosphorylation of MCM4 at Sites Inactivating DNA Helicase Activity of the MCM4-MCM6-MCM7 Complex during Epstein-Barr Virus Productive Replication. J. Virol., October 1, 2006; 80(20): 10064 - 10072. [Abstract] [Full Text] [PDF]

				L. A. Adang, C. H. Parsons, and D. H. Kedes Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection. J. Virol., October 1, 2006; 80(20): 10073 - 10082. [Abstract] [Full Text] [PDF]

				O. Moiseeva, F. A. Mallette, U. K. Mukhopadhyay, A. Moores, and G. Ferbeyre DNA Damage Signaling and p53-dependent Senescence after Prolonged beta-Interferon Stimulation Mol. Biol. Cell, April 1, 2006; 17(4): 1583 - 1592. [Abstract] [Full Text] [PDF]

				Y. C. Shin, H. Nakamura, X. Liang, P. Feng, H. Chang, T. F. Kowalik, and J. U. Jung Inhibition of the ATM/p53 Signal Transduction Pathway by Kaposi's Sarcoma-Associated Herpesvirus Interferon Regulatory Factor 1 J. Virol., March 1, 2006; 80(5): 2257 - 2266. [Abstract] [Full Text] [PDF]

				M. Gaspar and T. Shenk Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins PNAS, February 21, 2006; 103(8): 2821 - 2826. [Abstract] [Full Text] [PDF]

				C. Schelcher, S. Valencia, H.-J. Delecluse, M. Hicks, and A. J. Sinclair Mutation of a Single Amino Acid Residue in the Basic Region of the Epstein-Barr Virus (EBV) Lytic Cycle Switch Protein Zta (BZLF1) Prevents Reactivation of EBV from Latency J. Virol., November 1, 2005; 79(21): 13822 - 13828. [Abstract] [Full Text] [PDF]

				J. Dahl, J. You, and T. L. Benjamin Induction and Utilization of an ATM Signaling Pathway by Polyomavirus J. Virol., October 15, 2005; 79(20): 13007 - 13017. [Abstract] [Full Text] [PDF]

				N. Shirata, A. Kudoh, T. Daikoku, Y. Tatsumi, M. Fujita, T. Kiyono, Y. Sugaya, H. Isomura, K. Ishizaki, and T. Tsurumi Activation of Ataxia Telangiectasia-mutated DNA Damage Checkpoint Signal Transduction Elicited by Herpes Simplex Virus Infection J. Biol. Chem., August 26, 2005; 280(34): 30336 - 30341. [Abstract] [Full Text] [PDF]