1. Telomere uncapping duringin vitroT-lymphocyte senescence
- Author
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Martine Ffrench, Luc-Marie Gerland, Régine Catallo, Eric Gilson, Yves Tourneur, Aude Roborel de Climens, Serge Bauwens, Iwona Urbanowicz, Gilles Salles, Aurélie Belleville, Amel Chebel, and Wei Wen Chien
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,Senescence ,Aging ,Telomerase ,DNA damage ,T-Lymphocytes ,Lymphocyte ,Telomere-Binding Proteins ,Down-Regulation ,Biology ,Lymphocyte Activation ,Shelterin Complex ,Immunophenotyping ,Histones ,Mice ,medicine ,Animals ,Humans ,Cells, Cultured ,Cellular Senescence ,Cyclin-Dependent Kinase Inhibitor p16 ,Uncapping ,Aged ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Cycle ,Intracellular Signaling Peptides and Proteins ,Cell Biology ,Telomere ,Shelterin ,Molecular biology ,Cell biology ,medicine.anatomical_structure ,Tumor Suppressor p53-Binding Protein 1 ,Cell aging ,Cell Division - Abstract
Normal lymphocytes represent examples of somatic cells that are able to induce telomerase activity when stimulated. As previously reported, we showed that, during lymphocyte long-term culture and repeated stimulations, the appearance of senescent cells is associated with telomere shortening and a progressive drop in telomerase activity. We further showed that this shortening preferentially occured at long telomeres and was interrupted at each stimulation by a transitory increase in telomere length. In agreement with the fact that telomere uncapping triggers lymphocyte senescence, we observed an increase in gamma-H2AX and 53BP1 foci as well as in the percentage of cells exhibiting DNA damage foci in telomeres. Such a DNA damage response may be related to the continuous increase of p16(ink4a) upon cell stimulation and cell aging. Remarkably, at each stimulation, the expression of shelterin genes, such as hTRF1, hTANK1, hTIN2, hPOT1 and hRAP1, was decreased. We propose that telomere dysfunction during lymphocyte senescence caused by iterative stimulations does not only result from an excessive telomere shortening, but also from a decrease in shelterin content. These observations may be relevant for T-cell biology and aging.
- Published
- 2009