A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses

Lilley, C.E., Chaurushiya, M.S., Boutell, C. , Landry, S., Suh, J., Panier, S., Everett, R.D., Stewart, G.S., Durocher, D. and Weitzman, M.D. (2010) A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. EMBO Journal, 29(5), pp. 943-955. (doi: 10.1038/emboj.2009.400) (PMID:22405594) (PMCID:PMC3648639)

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Abstract

The ICP0 protein of herpes simplex virus type 1 is an E3 ubiquitin ligase and transactivator required for the efficient switch between latent and lytic infection. As DNA damaging treatments are known to reactivate latent virus, we wished to explore whether ICP0 modulates the cellular response to DNA damage. We report that ICP0 prevents accumulation of repair factors at cellular damage sites, acting between recruitment of the mediator proteins Mdc1 and 53BP1. We identify RNF8 and RNF168, cellular histone ubiquitin ligases responsible for anchoring repair factors at sites of damage, as new targets for ICP0-mediated degradation. By targeting these ligases, ICP0 expression results in loss of ubiquitinated forms of H2A, mobilization of DNA repair proteins and enhanced viral fitness. Our study raises the possibility that the ICP0-mediated control of histone ubiquitination may link DNA repair, relief of transcriptional repression, and activation of latent viral genomes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Everett, Professor Roger and Boutell, Dr Chris
Authors: Lilley, C.E., Chaurushiya, M.S., Boutell, C., Landry, S., Suh, J., Panier, S., Everett, R.D., Stewart, G.S., Durocher, D., and Weitzman, M.D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Journal Name:EMBO Journal
ISSN:0261-4189
ISSN (Online):1460-2075
Published Online:14 January 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656521The role of ubiquitin and ubiquitin-like proteins during viral infectionChris BoutellMedical Research Council (MRC)MC_UU_12014/5MVLS III - CENTRE FOR VIRUS RESEARCH