Endogenous retroelements as alarms for disruptions to cellular homeostasis

Endogenous retroelements are DNA sequences which can duplicate and move to new locations in the genome. Actively moving endogenous retroelements can be disruptive to the host, and their expression is therefore often repressed. Interestingly, drugs that disrupt the repression of endogenous retroelements show promise for treating cancer. Expressed endogenous retroelements can activate innate immune receptors that activate the antiviral response, potentially leading to the death of cancer cells. We discuss disruptions to cellular processes which can lead to activation of the antiviral state from endogenous retroelements, and present the ‘fire alarm hypothesis’, where we argue that endogenous retroelements act as alarms for disruptions to these cellular processes. Furthermore, we discuss the properties of endogenous retroelements which make them suitable as alarms.