Genome Instability Invites Murine Leukemia Virus Integration. Mus musculus

One of the consequences of retroviral integration into the host genome is insertional mutagenesis, a process that can lead to malignant transformation. Integration is not entirely random and favors open chromatin in highly transcribed regions of the genome, but how integration sites are selected is not precisely defined. Here, we analyze murine leukemia virus (MLV) integration libraries from mouse primary B cells in the presence and absence of activation induced cytidine deaminase (AID), a B lymphocyte specific enzyme that is associated with DNA damage. We find that a very significant proportion of retrovirus integration occurs at sites of DNA damage including AID target sites, early replication fragile sites (ERFs), and sites of targeted genome damage by the I-SceI meganuclease. High-resolution maps of the sites of virus integration further define the properties and boundaries of unstable regions of the genome. The data suggest that DNA damage is an important feature of retroviral integration site selection.