دورية أكاديمية
Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome
| العنوان: | Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome |
|---|---|
| المؤلفون: | Aguado J., Sola-Carvajal A., Cancila V., Revechon G., Ong P. F., Jones-Weinert C. W., Wallen Arzt E., Lattanzi G., Dreesen O., Tripodo C., Rossiello F., Eriksson M., d'Adda di Fagagna F. |
| المساهمون: | Aguado J., Sola-Carvajal A., Cancila V., Revechon G., Ong P.F., Jones-Weinert C.W., Wallen Arzt E., Lattanzi G., Dreesen O., Tripodo C., Rossiello F., Eriksson M., d'Adda di Fagagna F. |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2019 |
| المجموعة: | IRIS Università degli Studi di Palermo |
| مصطلحات موضوعية: | DNA damage, Hutchinson-Gilford Progeria Syndrome, Settore MED/08 - Anatomia Patologica |
| الوصف: | Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31740672; info:eu-repo/semantics/altIdentifier/wos/WOS:000496922600001; volume:10; issue:1; firstpage:4990; numberofpages:11; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/10447/395018Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85075114173; http://www.nature.com/ncomms/index.htmlTest |
| DOI: | 10.1038/s41467-019-13018-3 |
| الإتاحة: | https://doi.org/10.1038/s41467-019-13018-3Test http://hdl.handle.net/10447/395018Test http://www.nature.com/ncomms/index.htmlTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.77C29354 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-13018-3 |
|---|