File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Epstein-Barr virus BZLF1 protein impairs accumulation of host DNA damage proteins at damage sites in response to DNA damage

TitleEpstein-Barr virus BZLF1 protein impairs accumulation of host DNA damage proteins at damage sites in response to DNA damage
Authors
Issue Date2015
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/
Citation
Laboratory Investigation, 2015, v. 95 n. 8, p. 937-950 How to Cite?
AbstractEpstein–Barr virus (EBV) infection is closely associated with several human malignancies including nasopharyngeal carcinoma (NPC). The EBV immediate-early protein BZLF1 is the key mediator that switches EBV infection from latent to lytic forms. The lytic form of EBV infection has been implicated in human carcinogenesis but its molecular mechanisms remain unclear. BZLF1 has been shown to be a binding partner of several DNA damage response (DDR) proteins. Its functions in host DDR remain unknown. Thus, we explore the effects of BZLF1 on cellular response to DNA damage in NPC cells. We found that expression of BZLF1 impaired the binding between RNF8 and MDC1 (mediator of DNA damage checkpoint 1), which in turn interfered with the localization of RNF8 and 53BP1 to the DNA damage sites. The RNF8-53BP1 pathway is important for repair of DNA double-strand breaks and DNA damage-induced G2/M checkpoint activation. Our results showed that, by impairing DNA damage repair as well as abrogating G2/M checkpoint, BZLF1 induced genomic instability and rendered cells more sensitive to ionizing radiation. Moreover, the blockage of 53BP1 and RNF8 foci formation was recapitulated in EBV-infected cells. Taken together, our study raises the possibility that, by causing mis-localization of important DDR proteins, BZLF1 may function as a link between lytic EBV infection and impaired DNA damage repair, thus contributing to the carcinogenesis of EBV-associated human epithelial malignancies.
Persistent Identifierhttp://hdl.handle.net/10722/210683
ISSN
2015 Impact Factor: 4.202
2015 SCImago Journal Rankings: 2.133
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, J-
dc.contributor.authorDeng, W-
dc.contributor.authorHau, PM-
dc.contributor.authorLIU, J-
dc.contributor.authorLAU, MY-
dc.contributor.authorCheung, A-
dc.contributor.authorHuen, MSY-
dc.contributor.authorTsao, GSW-
dc.date.accessioned2015-06-23T05:46:32Z-
dc.date.available2015-06-23T05:46:32Z-
dc.date.issued2015-
dc.identifier.citationLaboratory Investigation, 2015, v. 95 n. 8, p. 937-950-
dc.identifier.issn0023-6837-
dc.identifier.urihttp://hdl.handle.net/10722/210683-
dc.description.abstractEpstein–Barr virus (EBV) infection is closely associated with several human malignancies including nasopharyngeal carcinoma (NPC). The EBV immediate-early protein BZLF1 is the key mediator that switches EBV infection from latent to lytic forms. The lytic form of EBV infection has been implicated in human carcinogenesis but its molecular mechanisms remain unclear. BZLF1 has been shown to be a binding partner of several DNA damage response (DDR) proteins. Its functions in host DDR remain unknown. Thus, we explore the effects of BZLF1 on cellular response to DNA damage in NPC cells. We found that expression of BZLF1 impaired the binding between RNF8 and MDC1 (mediator of DNA damage checkpoint 1), which in turn interfered with the localization of RNF8 and 53BP1 to the DNA damage sites. The RNF8-53BP1 pathway is important for repair of DNA double-strand breaks and DNA damage-induced G2/M checkpoint activation. Our results showed that, by impairing DNA damage repair as well as abrogating G2/M checkpoint, BZLF1 induced genomic instability and rendered cells more sensitive to ionizing radiation. Moreover, the blockage of 53BP1 and RNF8 foci formation was recapitulated in EBV-infected cells. Taken together, our study raises the possibility that, by causing mis-localization of important DDR proteins, BZLF1 may function as a link between lytic EBV infection and impaired DNA damage repair, thus contributing to the carcinogenesis of EBV-associated human epithelial malignancies.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/-
dc.relation.ispartofLaboratory Investigation-
dc.titleEpstein-Barr virus BZLF1 protein impairs accumulation of host DNA damage proteins at damage sites in response to DNA damage-
dc.typeArticle-
dc.identifier.emailYang, J: jiesarah@hku.hk-
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hk-
dc.identifier.emailHau, PM: tomhau10@hku.hk-
dc.identifier.emailCheung, A: lmcheung@hku.hk-
dc.identifier.emailHuen, MSY: huen.michael@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.authorityDeng, W=rp01640-
dc.identifier.authorityCheung, A=rp00332-
dc.identifier.authorityHuen, MSY=rp01336-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.doi10.1038/labinvest.2015.69-
dc.identifier.pmid26006018-
dc.identifier.scopuseid_2-s2.0-84938057293-
dc.identifier.hkuros243646-
dc.identifier.volume95-
dc.identifier.issue8-
dc.identifier.spage937-
dc.identifier.epage950-
dc.identifier.isiWOS:000358688600008-
dc.publisher.placeUnited Kingdom-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats