Genomic integrity and mitochondrial metabolism defects in Warsaw syndrome cells: a comparison with Fanconi anemia
| Autor: | Luisa M. R. Napolitano, Martina Moretti, Silvia Ravera, Viviana Chiappetta, Giuseppe Cortone, Nicoletta Zini, Barbara Crescenzi, Flavio Faletra, Roberta Bottega, Enrico Cappelli, Francesca M. Pisani, Michela Faleschini, Anna Savoia, Silvia Onesti, Silvia Arniani, Job de Lange, Cristina Mecucci, Fabio Sirchia, Barbara Medagli |
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| Přispěvatelé: | Human genetics |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genome instability Physiology Clinical Biochemistry Warsaw syndrome Kearns-Sayre Syndrome Mitochondrion Biology Genomic Instability Frameshift mutation DEAD-box RNA Helicases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine DDX11 Fanconi anemia medicine oxidative stress Humans Abnormalities Multiple Gene genomic integrity mitochondrial defects DNA Helicases Mitochondrial Myopathies Cell Biology Genomics medicine.disease Phenotype Cell biology 030104 developmental biology Fanconi Anemia chemistry 030220 oncology & carcinogenesis Mutation OXOPHOS DNA |
| Zdroj: | Journal of cellular physiology 236 (2021): 5664–5675. doi:10.1002/jcp.30265 info:cnr-pdr/source/autori:Bottega, Roberta; Ravera, Silvia; Napolitano, Luisa M. R.; Chiappetta, Viviana; Zini, Nicoletta; Crescenzi, Barbara; Arniani, Silvia; Faleschini, Michela; Cortone, Giuseppe; Faletra, Flavio; Medagli, Barbara; Sirchia, Fabio; Moretti, Martina; de Lange, Job; Cappelli, Enrico; Mecucci, Cristina; Onesti, Silvia; Pisani, Francesca M.; Savoia, Anna/titolo:Genomic integrity and mitochondrial metabolism defects in Warsaw syndrome cells: a comparison with Fanconi anemia./doi:10.1002%2Fjcp.30265/rivista:Journal of cellular physiology (Print)/anno:2021/pagina_da:5664/pagina_a:5675/intervallo_pagine:5664–5675/volume:236 Journal of Cellular Physiology, 236(8), 5664-5675. Wiley-Liss Inc. Bottega, R, Ravera, S, Napolitano, L M R, Chiappetta, V, Zini, N, Crescenzi, B, Arniani, S, Faleschini, M, Cortone, G, Faletra, F, Medagli, B, Sirchia, F, Moretti, M, de Lange, J, Cappelli, E, Mecucci, C, Onesti, S, Pisani, F M & Savoia, A 2021, ' Genomic integrity and mitochondrial metabolism defects in Warsaw syndrome cells : A comparison with Fanconi anemia ', Journal of Cellular Physiology, vol. 236, no. 8, pp. 5664-5675 . https://doi.org/10.1002/jcp.30265 |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | Warsaw breakage syndrome (WABS), is caused by biallelic mutations of DDX11, a gene coding a DNA helicase. We have recently reported two affected sisters, compound heterozygous for a missense (p.Leu836Pro) and a frameshift (p.Lys303Glufs*22) variant. By investigating the pathogenic mechanism, we demonstrate the inability of the DDX11 p.Leu836Pro mutant to unwind forked DNA substrates, while retaining DNA binding activity. We observed the accumulation of patient-derived cells at the G2/M phase and increased chromosomal fragmentation after mitomycin C treatment. The phenotype partially overlaps with features of the Fanconi anemia cells, which shows not only genomic instability but also defective mitochondria. This prompted us to examine mitochondrial functionality in WABS cells and revealed an altered aerobic metabolism. This opens the door to the further elucidation of the molecular and cellular basis of an impaired mitochondrial phenotype and sheds light on this fundamental process in cell physiology and the pathogenesis of these diseases. |
| Databáze: | OpenAIRE |
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