Ribonucleases (RNAses) H are enzymes that hydrolyze the RNA strands of RNA/DNA hybrids. The major role of these enzymes is to remove the RNA strand from the RNA/DNA hybrids that form during DNA replication and repair. RNAse H2 is made up of three subunits; all three are required for RNAse activity. Recent evidence has demonstrated that mutations in RNAse H2A or any of the other subunits result in Aicardi-Goutieres syndrome (AGS), a neurological disorder with similar symptoms to viral brain infections including high levels of IFN-alpha in the cerebral spinal fluid. Similar conditions are observed with mutations in TREX1, a single-stranded DNA exonuclease, suggesting that RNAse H2 and TREX1 may have similar roles, and that mutations in any of these genes lead to an accumulation of intracellular nucleic acids, triggering an inflammatory response through activation of the innate immune system.
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