Mis-segregated chromosomes end up in micronuclei and chromosome bridges, whose envelopes rupture and expose DNA to the cytoplasm. There the sensor cGAS reads it as a danger signal and triggers type I interferon.
We showed that the exonuclease TREX1 degrades this DNA from the endoplasmic reticulum, that a protein barrier at ruptured micronuclei governs access to it, and that tumors induce TREX1 to shield themselves from immune surveillance. Removing TREX1 restores antitumor immunity in tumors able to respond.
Read more at maciejowskilab.org.
