The relevance of ssDNA intermediates in humans is highlighted by the Aicardi–Goutières syndrome patients and mice that carry inborn defects in TREX1 (Three prime repair exonuclease 1); TREX1 degrades ssDNA polynucleotide species derived from the processing of aberrant DNA replication intermediates to prevent persistent DDR activation (Yang et al., 2007). Here, TREX1 is linked to Aicardi-Goutières syndrome.