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A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses
Author(s) -
Lilley Caroline E,
Chaurushiya Mira S,
Boutell Chris,
Landry Sebastien,
Suh Junghae,
Panier Stephanie,
Everett Roger D,
Stewart Grant S,
Durocher Daniel,
Weitzman Matthew D
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.400
Subject(s) - biology , ubiquitin ligase , ubiquitin , histone , dna damage , histone h2a , microbiology and biotechnology , cancer research , dna , genetics , gene
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.