Authors: Rossi, Giacomina | Conconi, Donatella | Panzeri, Elena | Redaelli, Serena | Piccoli, Elena | Paoletta, Laura | Dalprà, Leda | Tagliavini, Fabrizio
Article Type:
Research Article
Abstract:
In addition to the main function of promoting polymerization and stabilization of microtubules, other roles are being attributed to tau, now considered a multifunctional protein. In particular, previous studies suggest that tau is involved in chromosome stability and genome protection. We performed cytogenetic analysis, including molecular karyotyping, on lymphocytes and fibroblasts from patients affected by frontotemporal lobar degeneration carrying different mutations in the microtubule-associated protein tau gene, to investigate the effects of these mutations on genome stability. Furthermore, we analyzed the response of mutated lymphoblastoid cell lines to genotoxic agents to evaluate the participation of tau to DNA repair systems.
…We found a significantly higher level of chromosome aberrations in mutated than in control cells. Mutated lymphocytes showed higher percentages of stable lesions, clonal and total aneuploidy (medians: 2 versus 0, p ≪ 0.01; 1.5 versus 0, p ≪ 0.01; 16.5 versus 0, p ≪ 0.01, respectively). Fibroblasts of patients showed higher percentages of stable lesions, structural aberrations and total aneuploidy (medians: 0 versus 0, p = 0.03; 5.8 versus 0, p = 0.02; 26.5 versus 12.6, p ≪ 0.01, respectively). In addition, the in depth analysis of DNA copy number variations showed a higher tendency to non-allelic homologous recombination in mutated cells. Finally, while our analysis did not support an involvement of tau in DNA repair systems, it revealed its role in stabilization of chromatin. In summary, our findings indicate a role of tau in genome and chromosome stability that can be ascribed to its function as a microtubule-associated protein as well as a protein protecting chromatin integrity through interaction with DNA.
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Keywords: Chromosome aberrations, DNA copy number variations, genome instability, MAPT, mutation, tau protein, tauopathies
DOI: 10.3233/JAD-2012-121633
Citation: Journal of Alzheimer's Disease,
vol. 33, no. 4, pp. 969-982, 2013
Price: EUR 27.50
