Positive regulation of DNA double strand break repair activity during differentiation of long life span cells: the example of adipogenesis
| Autor: | Aline Meulle, Bernard Salles, Catherine Muller, Philippe Valet, Danièle Daviaud |
|---|---|
| Přispěvatelé: | Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
DNA Repair
MESH: 3T3 Cells Cellular differentiation MESH: DNA Breaks Double-Stranded lcsh:Medicine DNA-Activated Protein Kinase Mice chemistry.chemical_compound 0302 clinical medicine Adipocytes DNA Breaks Double-Stranded MESH: Animals lcsh:Science Cellular Senescence MESH: DNA Repair Biochemistry/Replication and Repair 0303 health sciences Adipogenesis Multidisciplinary Nuclear Proteins Genetics and Genomics/Gene Expression Antigens Nuclear Cell Differentiation Cell Biology/Cellular Death and Stress Responses 3T3 Cells Double Strand Break Repair DNA-Binding Proteins Non-homologous end joining Histone MESH: Cell Aging 030220 oncology & carcinogenesis Research Article MESH: Cell Differentiation DNA repair DNA damage Biology 03 medical and health sciences [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Ku Autoantigen MESH: Mice MESH: Antigens Nuclear MESH: Adipocytes 030304 developmental biology MESH: Humans lcsh:R Molecular biology enzymes and coenzymes (carbohydrates) chemistry biology.protein MESH: DNA-Activated Protein Kinase lcsh:Q MESH: Nuclear Proteins MESH: Adipogenesis DNA MESH: DNA-Binding Proteins |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2008, 3 (10), pp.e3345. ⟨10.1371/journal.pone.0003345⟩ PLoS ONE, 2008, 3 (10), pp.e3345. ⟨10.1371/journal.pone.0003345⟩ PLoS ONE, Vol 3, Iss 10, p e3345 (2008) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0003345⟩ |
| Popis: | International audience; Little information is available on the ability of terminally differentiated cells to efficiently repair DNA double strand breaks (DSBs), and one might reasonably speculate that efficient DNA repair of these threatening DNA lesions, is needed in cells of long life span with no or limited regeneration from precursor. Few tissues are available besides neurons that allow the study of DNA DSBs repair activity in very long-lived cells. Adipocytes represent a suitable model since it is generally admitted that there is a very slow turnover of adipocytes in adult. Using both Pulse Field Gel Electrophoresis (PFGE) and the disappearance of the phosphorylated form of the histone variant H2AX, we demonstrated that the ability to repair DSBs is increased during adipocyte differentiation using the murine pre-adipocyte cell line, 3T3F442A. In mammalian cells, DSBs are mainly repaired by the non-homologous end-joining pathway (NHEJ) that relies on the DNA dependent protein kinase (DNA-PK) activity. During the first 24 h following the commitment into adipogenesis, we show an increase in the expression and activity of the catalytic sub-unit of the DNA-PK complex, DNA-PKcs. The increased in DNA DSBs repair activity observed in adipocytes was due to the increase in DNA-PK activity as shown by the use of DNA-PK inhibitor or sub-clones of 3T3F442A deficient in DNA-PKcs using long term RNA interference. Interestingly, the up-regulation of DNA-PK does not regulate the differentiation program itself. Finally, similar positive regulation of DNA-PKcs expression and activity was observed during differentiation of primary culture of pre-adipocytes isolated from human sub-cutaneous adipose tissue.Our results show that DNA DSBs repair activity is up regulated during the early commitment into adipogenesis due to an up-regulation of DNA-PK expression and activity. In opposition to the general view that DNA DSBs repair is decreased during differentiation, our results demonstrate that an up-regulation of this process might be observed in post-mitotic long-lived cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|