DNA Mismanagement Leads to Immune System Oversight

Trex1, a major 3′ DNA exonuclease in mammalian cells, has been thought to act primarily in DNA replication or repair. Surprisingly, the major phenotype resulting from Trex1 deficiency in humans and mice is a chronic inflammatory disease. In this issue, report that Trex1 deficiency causes chronic activation of the ATM-dependent DNA-damage checkpoint and accumulation of a discrete single-stranded DNA species in the cytoplasm, either of which could contribute to chronic inflammation.