Article
TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks.
Cell reports - 28 May 2024
Geraud Mathéa, Cristini Agnese, Salimbeni Simona, Bery Nicolas, Jouffret Virginie, Russo Marco, Ajello Andrea Carla, Fernandez Martinez Lara, Marinello Jessica, Cordelier Pierre, Trouche Didier, Favre Gilles, Nicolas Estelle, Capranico Giovanni, Sordet Olivier
Abstract excerpt
TDP1 removes transcription-blocking topoisomerase I cleavage complexes (TOP1ccs), and its inactivating H493R mutation causes the neurodegenerative syndrome SCAN1. However, the molecular mechanism underlying the SCAN1 phenotype is unclear. Here, we generate human SCAN1 cell models using CRISPR-Cas9 and show that they accumulate TOP1ccs along with changes in gene expression and genomic distribution of R-loops....
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