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Transcriptional effects of TDP1 deficiency in non-replicating U2OS cells

GSE186693 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2024/04/30 Platform GPL20301
Summary
Spinocerebellar ataxia with axonal neuropathy (SCAN1) is a rare recessive neurodegenerative syndrome associated with cerebellar atrophy and peripheral neuropathy. It is caused by a homozygous missense mutation in the tyrosyl-DNA phosphodiesterase-1 (TDP1) gene (A1478G). resulting in a substitution of histidine for arginine-493 (H493R) in the TDP1 catalytic site, leading to reduced TDP1 activity. How TDP1 H493R mutation promotes the SCAN1 phenotype, which is associated with the death of post-mitotic neurons, is unclear. We have generated models of osteosarcoma U2OS cells homozygous for TDP1 H493R employing the CRISPR-Cas9 technique (2 clones, named “1P” and “3.3”). Here, we have generated transcriptional genome wide profile in order to characterize differences in gene expression that are specific of TDP1-mutated clones.
Published in
TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks
Geraud M, Cristini A, Salimbeni S et al. · Cell reports 2024 · PMID 38761375 · doi:10.1016/j.celrep.2024.114214
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Also filed as BioProject PRJNA775084 and SRA study SRP343438. Searching any of these in the dataset finder brings you back here.

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