Loss of SORCS2 is associated with neuronal DNA double-strand breaks
Loss of SORCS2 is associated with neuronal DNA double-strand breaks
Abstract SORCS2 is one of five proteins that constitute the Vps10p-domain receptor family. Members of this family play important roles in cellular processes linked to neuronal survival, differentiation and function. Genetic and functional studies implicate SORCS2 in cognitive function, as well as in neurodegenerative and psychiatric disorders. DNA damage and DNA repair deficits are linked to ageing and neurodegeneration, and transient neuronal DNA double-strand breaks (DSBs) also occur as a result of neuronal activity. Here, we report a novel role for SORCS2 in DSB formation. We show that SorCS2 loss is associated with elevated DSB levels in the mouse dentate gyrus and that knocking out SORCS2 in a human neuronal cell line increased Topoisomerase IIβ-dependent DSB formation and reduced neuronal viability. Neuronal stimulation had no impact on levels of DNA damage, suggesting that the observed differences are unlikely to be the result of aberrant neuronal activity. Our findings are consistent with studies linking the VPS10 receptors and DNA damage to neurodegenerative conditions.
Kaas Mathias、Anderson Susan M.、Walker Rosie M.、Payne Abigail L.、Giannopoulos Panagiotis、Abbott Catherine M.、Porteous David J.、Olsen Ditte、Evans Kathryn L.、Phillips Jonathan、Spires-Jones Tara L.、Gospodinova Katerina O.、Glerup Simon、Pandya Divya、Bermingham Mairead L.
Department of Biomedicine, Aarhus UniversityCentre for Genomic and Experimental Medicine, University of EdinburghCentre for Genomic and Experimental Medicine, University of Edinburgh||Chancellor?ˉs Building, 49 University of EdinburghCentre for Genomic and Experimental Medicine, University of EdinburghCentre for Genomic and Experimental Medicine, University of EdinburghCentre for Genomic and Experimental Medicine, University of EdinburghCentre for Genomic and Experimental Medicine, University of EdinburghDepartment of Biomedicine, Aarhus UniversityCentre for Genomic and Experimental Medicine, University of EdinburghCentre for Genomic and Experimental Medicine, University of EdinburghCentre for Discovery Brain Sciences, UK Dementia Research Institute, University of EdinburghCentre for Genomic and Experimental Medicine, University of EdinburghDepartment of Biomedicine, Aarhus UniversityCentre for Genomic and Experimental Medicine, University of EdinburghCentre for Genomic and Experimental Medicine, University of Edinburgh
基础医学神经病学、精神病学分子生物学
SORCS2DNA double-strand breaksneuronal activityneurodegeneration
Kaas Mathias,Anderson Susan M.,Walker Rosie M.,Payne Abigail L.,Giannopoulos Panagiotis,Abbott Catherine M.,Porteous David J.,Olsen Ditte,Evans Kathryn L.,Phillips Jonathan,Spires-Jones Tara L.,Gospodinova Katerina O.,Glerup Simon,Pandya Divya,Bermingham Mairead L..Loss of SORCS2 is associated with neuronal DNA double-strand breaks[EB/OL].(2025-03-28)[2025-07-09].https://www.biorxiv.org/content/10.1101/2021.04.28.441600.点此复制
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