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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

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