Methylated TRF2 associates with the nuclear matrix and serves as a potential biomarker for cellular senescence
| Autor: | Taylor R. H. Mitchell, Xu-Dong Zhu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Senescence
Aging DNA damage Fluorescent Antibody Technique TRF2 Biology Transfection Methylation Cell Line 03 medical and health sciences 0302 clinical medicine cellular senescence Humans Telomeric Repeat Binding Protein 2 Cellular localization 030304 developmental biology 0303 health sciences Cell Biology Telomere Shelterin Nuclear matrix Molecular biology arginine methylation 030220 oncology & carcinogenesis nuclear matrix Research Perspective Cell aging Biomarkers |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Methylation of N-terminal arginines of the shelterin component TRF2 is important for cellular proliferation. While TRF2 is found at telomeres, where it plays an essential role in maintaining telomere integrity, little is known about the cellular localization of methylated TRF2. Here we report that the majority of methylated TRF2 is resistant to extraction by high salt buffer and DNase I treatment, indicating that methylated TRF2 is tightly associated with the nuclear matrix. We show that methylated TRF2 drastically alters its nuclear staining as normal human primary fibroblast cells approach and enter replicative senescence. This altered nuclear staining, which is found to be overwhelmingly associated with misshapen nuclei and abnormal nuclear matrix folds, can be suppressed by hTERT and it is barely detectable in transformed and cancer cell lines. We find that dysfunctional telomeres and DNA damage, both of which are potent inducers of cellular senescence, promote the altered nuclear staining of methylated TRF2, which is dependent upon the ATM-mediated DNA damage response. Collectively, these results suggest that the altered nuclear staining of methylated TRF2 may represent ATM-mediated nuclear structural alteration associated with cellular senescence. Our data further imply that methylated TRF2 can serve as a potential biomarker for cellular senescence. |
| Databáze: | OpenAIRE |
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