NDLI: A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells

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A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells

Content Provider	Scilit
Author	Machado-Pinilla, Rosario Sánchez-Pérez, Isabel Murguía, José Ramón Sastre, Leandro Perona, Rosario
Copyright Year	2008
Description	Dyskerin gene is mutated in patients with X-linked dyskeratosis congenita (X-DC), which results in greatly reduced levels of telomerase activity. A genetic suppressor element (GSE) termed GSE24-2 has been isolated in a screening for cisplatin resistance. GSE24-2–expressing cells presented impaired telomerase inhibition following in vitro exposure to chemotherapies, such as cisplatin, or telomerase inhibitors. The promoter of the telomerase component hTERT was constitutively activated in GSE24-2 cells in a c-myc expression–dependent manner. Deletion analyses and mutagenesis of the human c-myc promoter demonstrated that the target sequence for activation was the nuclease hypersensitive element-III (NHEIII) site located upstream to the P1 region of the promoter. Further, expression of GSE24-2 in cell lines derived from patients with X-DC and in VA13 cells induced increased hTERT RNA and hTR levels and recovery of telomerase activity. Finally, expression of GSE24-2 was able to rescue X-DC fibroblasts from premature senescence. These data demonstrate that this domain of dyskerin plays an important role in telomerase maintenance following cell insults such as cisplatin treatment, and in telomerase-defective cells in patients with X-DC. The expression of this dyskerin fragment has a dominant function in X-DC cells and could provide the basis for a therapeutic approach to this disease.
Related Links	http://www.bloodjournal.org/content/bloodjournal/111/5/2606.full.pdf
Ending Page	2614
Page Count	9
Starting Page	2606
DOI	10.1182/blood-2007-04-083261
Journal	Blood
Issue Number	5
Volume Number	111
Language	English
Publisher	American Society of Hematology
Publisher Date	2008-03-01
Access Restriction	Open
Subject Keyword	Biochemistry and Molecular Biology X Dc Cisplatin Dyskerin Gse24 Telomerase Activity Patients with X Htert Chemotherapies Journal: Blood (Vol- 84, Issue- 5)
Content Type	Text
Resource Type	Article

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