Dataset Information


Impaired DNA damage metabolism promotes autoimmunity in TREX1 deficiency 

ABSTRACT: Constitutive low level DNA damage is linked to innate immune activation. Hierarchical clustering of over 9000 transcripts revealed remarkably similar profiles in a patient with lupus erythematosus and a patient with AGS with up-regulation of genes involved in DNA damage signaling, p53-inducible genes, senescence-associated genes as well as up-regulation of interferon-stimulated genes. Transcriptional profiling of fibroblasts exposed to oxidative stress showed a marked up-regulation of genes involved in DNA replication/repair and replication licensing in TREX1-deficient cells compared to wild type cells suggesting massive replication stress. Comparison of transcriptional profiles of unstressed patient fibroblasts with wild type cells as well as fibroblasts exposed to oxidative stress

ORGANISM(S): Homo sapiens  

SUBMITTER: Min Ae Lee-Kirsch   Min A Lee-Kirsch  Manuela Dobrick-Mattheuer  Dimitra Alexopoulou  M C Cardoso  Dagmar Wieczorek  Alexander Rapp  Stefanie Kretschmer  Christine Wolf  Andreas Dahl  Claudia Günther  Nicole Berndt  Claudia Krug  Thomas Kurth 

PROVIDER: E-GEOD-59233 | ArrayExpress | 2016-05-30



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Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent ty  ...[more]

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