Herpes simplex virus 1 (HSV-1) replicates in the nucleus and induces chromosomal DNA damage, including DNA double-strand breaks (DSBs). Host cells repair DSBs by non-homologous end joining (NHEJ) or homologous recombination, but how the cell chooses between these pathways and the impact of this decision on viral replication has been unclear. Karttunen et al. now show that HSV-1 inhibits NHEJ by triggering the Fanconi anaemia pathway. HSV-1 infection induced mono-ubiquitination of the two Fanconi anaemia pathway effectors, FANCI and FANCI-D2, which resulted in their redistribution from sites of DNA damage to viral replication compartments. Furthermore, HSV-1 replication was severely reduced in cells lacking components of the Fanconi anaemia pathway, and inhibition of NHEJ in these cells was sufficient to restore viral growth. These data suggest that HSV-1 manipulates the Fanconi anaemia pathway to suppress NHEJ and promote viral replication.
References
Karttunen, H. et al. Co-opting the Fanconi anemia genomic stability pathway enables herpesvirus DNA synthesis and productive growth. Mol. Cell 55, 111–122 (2014)
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Nunes-Alves, C. Manipulation of DNA repair pathways. Nat Rev Microbiol 12, 530 (2014). https://doi.org/10.1038/nrmicro3320
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DOI: https://doi.org/10.1038/nrmicro3320