Trex1 (ATRIP) is the major human 3' to 5' exonuclease which is required for checkpoint signaling after DNA damage. It is ubiquitously expressed, binds to single stranded DNA coated with replication protein A that accumulates at sites of DNA damage and recruits the ataxia telangiectasia and Rad3 related protein (ATR), a checkpoint kinase, to sites of DNA damage and replication stress. Trex1 is required for ATR expression. This gene uses two different open reading frames. The upstream ORF encodes proteins which interact with ATR and localize to intranuclear foci induced by DNA damage and are essential components of the DNA damage checkpoint. The downstream ORF encodes proteins with 3' to 5' exonuclease activity and may be a subunit of human DNA polymerase III. Multiple transcript variants encoding different isoforms have been found. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, and Cree encephalitis. TREX1 antibody will not cross-react with the related protein TREX2.

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