Your browser doesn't support javascript.
loading
CCAR1 promotes DNA repair via alternative splicing.
Karasu, Mehmet E; Jahnke, Leonard; Joseph, Brian J; Amerzhanova, Yerkezhan; Mironov, Aleksei; Shu, Xuan; Schröder, Markus S; Gvozdenovic, Ana; Sala, Irene; Zavolan, Mihaela; Jonas, Stefanie; Corn, Jacob E.
Afiliação
  • Karasu ME; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Jahnke L; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Joseph BJ; Department of Pathology and Cell Biology, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA.
  • Amerzhanova Y; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Mironov A; Computational and Systems Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.
  • Shu X; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Schröder MS; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Gvozdenovic A; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Sala I; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Zavolan M; Computational and Systems Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.
  • Jonas S; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
  • Corn JE; Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland. Electronic address: jacob.corn@biol.ethz.ch.
Mol Cell ; 84(14): 2634-2647.e9, 2024 Jul 25.
Article em En | MEDLINE | ID: mdl-38964321
ABSTRACT
DNA repair is directly performed by hundreds of core factors and indirectly regulated by thousands of others. We massively expanded a CRISPR inhibition and Cas9-editing screening system to discover factors indirectly modulating homology-directed repair (HDR) in the context of ∼18,000 individual gene knockdowns. We focused on CCAR1, a poorly understood gene that we found the depletion of reduced both HDR and interstrand crosslink repair, phenocopying the loss of the Fanconi anemia pathway. CCAR1 loss abrogated FANCA protein without substantial reduction in the level of its mRNA or that of other FA genes. We instead found that CCAR1 prevents inclusion of a poison exon in FANCA. Transcriptomic analysis revealed that the CCAR1 splicing modulatory activity is not limited to FANCA, and it instead regulates widespread changes in alternative splicing that would damage coding sequences in mouse and human cells. CCAR1 therefore has an unanticipated function as a splicing fidelity factor.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Processamento Alternativo / Proteína do Grupo de Complementação A da Anemia de Fanconi Limite: Animals / Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Processamento Alternativo / Proteína do Grupo de Complementação A da Anemia de Fanconi Limite: Animals / Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Suíça