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DNA Repair (Amst). 2008 Jun 1;7(6):997-1003. doi: 10.1016/j.dnarep.2008.02.010. Epub 2008 Apr 10.

TREX1 DNA exonuclease deficiency, accumulation of single stranded DNA and complex human genetic disorders.

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  • 1Genome Damage & Stability Centre, University of Sussex, Falmer, Brighton, East Sussex BN1 9RQ, UK. <>


Aicardi-Goutieres syndrome (AGS) is an unusual condition that clinically mimics a congenital viral infection. Several genes have recently been implicated in the aetiology of this disorder. One of these genes encodes the DNA exonuclease TREX1. Recent work from Yang, Lindahl and Barnes has provided insight into the cellular consequence of TREX1-deficiency. They found that TREX1-deficiency resulted in the intracellular accumulation of single stranded DNA resulting in chronic activation of the DNA damage response network, even in cells from Trex1-mutated AGS patients. Here, I summarise their findings and discuss them in context with the other AGS causative genes which encode subunits of the RNase H2 complex. I describe mechanisms by which the inappropriate intracellular accumulation of nucleic acid species might deleteriously impact upon normal cell cycle progression. Finally, using the example of Systemic Lupus Erythematosus (SLE), I also summarise the evidence suggesting that the failure to process intermediates of nucleic acid metabolism can result in the activation of uncontrolled autoimmunity.

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