New York University, Abu Dhabi
Host: Darcy Kelley
Title: Attacked from Within: How retrotransposon activation caused by epigenetic damage mimics infection and triggers an immune response
Abstract: Complex cytoplasmic nucleotide sensing mechanisms can recognize foreign DNA based on its lack of methylation and initiate an immune response to clear the infection. Loss of DNA methylation, a common feature of cancer cells and are part of distinct stages of embryonic development, and it is unclear how transposon repression or derepression in these conditions is managed. Our work using zebrafish embryos with global DNA hypomethylation caused by mutations in the Ubiquitin-like, with PHD and RING finger domains 1 (uhrf1) or DNA methyltransferase 1 (dnmt1) genes has discovered a robust immune response characteristic of viral infection, which is triggered by activation of retrotransposons. This finding shows that antiviral pathways as a mechanism to detect cells with intragenomic parasites activated by epigenetic damage, which implicates this as a major pathway in cancer.