ER-tethering directs TREX1 penetration of a BAF-dependent barrier at micronuclei - PubMed
3 hours ago
- #micronuclei
- #TREX1
- #BAF
- Micronuclei form due to chromosome segregation errors and their membrane collapse allows access to cGAS and TREX1.
- TREX1 requires ER-tethering to invade ruptured micronuclei, with BAF identified as a key regulator of this process.
- BAF accumulates at micronuclei post-collapse, enhancing TREX1 recruitment via LEM-domain protein interactions.
- In BAF-deficient cells, TREX1 shows delayed entry but increased DNA degradation and independence from ER-tethering.
- Recombinant BAF inhibits TREX1 DNA degradation in vitro by binding DNA, similarly outcompeting cGAS for micronuclear DNA.
- BAF creates a protective barrier limiting DNA-binding protein entry into micronuclei, explaining TREX1's ER-tethering necessity for immune suppression in chromosomally unstable cells.