Mediated Repair of Transcribed Genes Is Linked to SCA3 Pathogenesis
Deficiency in classical nonhomologous end-joining– mediated repair of transcribed genes is linked to SCA3 pathogenesis Anirban Chakrabortya, Nisha Tapryala, Tatiana Venkovaa,1, Joy Mitrab, Velmarini Vasquezb, Altaf H. Sarkerc, Sara Duarte-Silvad,e, Weihan Huaif, Tetsuo Ashizawag, Gourisankar Ghoshf, Patricia Macield,e, Partha S. Sarkarh, Muralidhar L. Hegdeb, Xu Cheni, and Tapas K. Hazraa,2 aDepartment of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Texas Medical Branch, Galveston, TX 77555; bDepartment of Neurosurgery, Center for Neuroregeneration, The Houston Methodist Research Institute, Houston, TX 77030; cDepartment of Cancer and DNA Damage Responses, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; dSchool of Medicine, Life and Health Sciences Research Institute, University of Minho, 4710-057 Braga, Portugal; eICVS (Life and Health Sciences Research Institute)/3B’s-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal; fDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093; gDepartment of Neurology, The Houston Methodist Research Institute, Houston, TX 77030; hDepartment of Neurology and Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555; and iDepartment of Neurosciences, University of California San Diego, La Jolla, CA 92093 Edited by James E. Cleaver, University of California San Francisco Medical Center, San Francisco, CA, and approved March 2, 2020 (received for review October 6, 2019) Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited ATXN3 knockout mice showed an increase in total ubiquitinated neurodegenerative disease caused by CAG (encoding glutamine) protein levels (19). Consistently, knockdown of ATXN3 resulted in repeat expansion in the Ataxin-3 (ATXN3) gene.
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