Altered splicing in exon 8 of the DNA replication factor CIZ1 affects subnuclear distribution and is associated with Alzheimer's disease |
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| Authors: | Dahmcke Christina Mackeprang Büchmann-Møller Stine Jensen Niels A Mitchelmore Cathy |
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| Affiliation: | aEucaryotic Cell Biology Research Group, Department of Science, Roskilde University, Roskilde, Denmark;bInstitute of Cell Biology, Zurich University, 8093, Switzerland;cMolecular Neurobiology Laboratory, Medical Biotechnology Center, University of Southern Denmark, J.B. Winslowsvej 25, Odense C, Denmark |
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| Abstract: | In order to understand the gene-mediated processes underlying sporadic Alzheimer's disease (AD), we carried out a subtractive cloning screen for novel AD candidate genes. We identified the gene encoding the DNA replication factor CIZ1 (CDKN1A interacting zinc finger protein 1) as being more highly expressed in Alzheimer tissue than in healthy brains. We show here that an isoform of CIZ1 which lacks a glutamine-rich region, due to alternative splicing in exon 8, is upregulated in AD brains relative to the full-length CIZ1 protein. We demonstrate for the first time that a minimal 28 amino acid sequence within this region is required for CIZ1 to associate with the nuclear matrix and to form nuclear foci. |
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| Keywords: | CDKN1A Nuclear matrix Alzheimer's disease DNA replication |
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