A structural characterization of in situ chromatin on cell lines isolated from patients affected by ataxia telangiectasia.
Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by numerous clinical and cellular features. The pleiotropic nature of the AT syndrome attests to the multiple roles of ATM, the protein codified by the gene altered in AT patients. We investigated if different mutations of ATM could reflect on different alterations of nuclear architecture and chromatin organization. We selected three lymphoblastoid cell lines isolated from AT patients affected by different mutations of ATM gene and one healthy control. We characterized the in situ chromatin structure of each cell line by a biophysical approach: (1) we evaluated the rearrangements of the chromatin domains at the level of single cell by quantitative fluorescence microscopy; (2) we analysed the changes of the average chromatin condensation by differential scanning calorimetry. The results show that the three different ATM mutations produce significant modifications of both nuclear architecture and chromatin condensation.
Department of Biophysical M&O Sciences and Technologies, University of Genova Medical School, Corso Europa 30, 16132 Genoa, Italy.
Myriam
M
Grattarola
Sara
S
Spaggiari
Luciana
L
Chessa
Camilla
C
Savio
Claudio
C
Nicolini
Laura
L
Vergani
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins; D002152:Calorimetry, Differential Scanning; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D002843:Chromatin / Q000737:chemistry* / Q000648:ultrastructure; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins; D006801:Humans; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012016:Reference Values; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases