Document Detail

Mutations in MAPT gene cause chromosome instability and introduce copy number variations widely in the genome.
MedLine Citation:
PMID:  23047372     Owner:  NLM     Status:  MEDLINE    
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 $\ll$ 0.01; 1.5 versus 0, p $\ll$ 0.01; 16.5 versus 0, p $\ll$ 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 $\ll$ 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.
Giacomina Rossi; Donatella Conconi; Elena Panzeri; Serena Redaelli; Elena Piccoli; Laura Paoletta; Leda Dalprà; Fabrizio Tagliavini
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  33     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-10-17     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  969-82     Citation Subset:  IM    
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MeSH Terms
Cell Line, Transformed
Cells, Cultured
Child, Preschool
Chromatin / genetics
Chromosomal Instability / genetics*
DNA Copy Number Variations / genetics*
Fibroblasts / chemistry,  physiology
Genome, Human / genetics*
Middle Aged
Mutation / genetics*
Young Adult
tau Proteins / genetics*
Grant Support
Reg. No./Substance:
0/Chromatin; 0/MAPT protein, human; 0/tau Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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