TREX1 Dominant Mutations in Lupus and Aicardi-Goutieres Syndrome
نویسندگان
چکیده
Jason M. Fye, Clinton D. Orebaugh, Stephanie R. Coffin, Thomas Hollis, and Fred W. Perrino From the Department of Biochemistry, Wake Forest School of Medicine Winston-Salem, North Carolina 27157 Running head: TREX1 degrades dsDNA Address correspondence to: Fred W. Perrino, PhD, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, Tel. 336–716–4349; Fax. 336–716–7671; E-mail: [email protected]
منابع مشابه
Aicardi–Goutières syndrome protein TREX1 suppresses L1 and maintains genome integrity through exonuclease-independent ORF1p depletion
Maintaining genome integrity is important for cells and damaged DNA triggers autoimmunity. Previous studies have reported that Three-prime repair exonuclease 1(TREX1), an endogenous DNA exonuclease, prevents immune activation by depleting damaged DNA, thus preventing the development of certain autoimmune diseases. Consistently, mutations in TREX1 are linked with autoimmune diseases such as syst...
متن کاملThe TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease.
Mutations in TREX1 have been linked to a spectrum of human autoimmune diseases including Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus, and retinal vasculopathy and cerebral leukodystrophy. A common feature in these conditions is the frequent detection of antibodies to double-stranded DNA (dsDNA). TREX1 participates in a cell death process implic...
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Detection of nucleic acids and induction of type I interferons (IFNs) are principal elements of antiviral defense but can cause autoimmunity if misregulated. Cytosolic DNA detection activates a potent, cell-intrinsic antiviral response through a poorly defined pathway. In a screen for proteins relevant to this IFN-stimulatory DNA (ISD) response, we identify 3' repair exonuclease 1 (Trex1). Muta...
متن کاملGenome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi–Goutières syndrome
Aicardi-Goutières syndrome (AGS) is a severe childhood inflammatory disorder that shows clinical and genetic overlap with systemic lupus erythematosus (SLE). AGS is thought to arise from the accumulation of incompletely metabolized endogenous nucleic acid species owing to mutations in nucleic acid-degrading enzymes TREX1 (AGS1), RNase H2 (AGS2, 3 and 4), and SAMHD1 (AGS5). However, the identity...
متن کاملClinical heterogeneity among a three-generation Japanese family with D18N TREX1 mutation for Aicardi-Goutières syndrome / familial chilblain lupus
Background Aicardi-Goutières syndrome (AGS) is a genetic disease, characterized by encephalopathy with cerebral calcification, white matter abnormalities, cerebral atrophy, elevated interferon-alpha in the cerebrospinal fluid and chilblain. Most of AGS patients have severe neurological findings including developmental delay. Five genes, namely TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1 have be...
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