Biomaterial Database

Human RTEL1 stabilizes long G-overhangs allowing telomerase-dependent over-extension. 2018

Rosa M Porreca, and Galina Glousker, and Aya Awad, and Maria I Matilla Fernandez, and Anne Gibaud, and Christian Naucke, and Scott B Cohen, and Tracy M Bryan, and Yehuda Tzfati, and Irena Draskovic, and Arturo Londoño-Vallejo

Institut Curie, PSL Research University, Sorbonne Universités, CNRS UMR3244 Telomere and cancer lab, 75005 Paris, France.

Telomere maintenance protects the cell against genome instability and senescence. Accelerated telomere attrition is a characteristic of premature aging syndromes including Dyskeratosis congenita (DC). Mutations in hRTEL1 are associated with a severe form of DC called Hoyeraal-Hreidarsson syndrome (HHS). HHS patients carry short telomeres and HHS cells display telomere damage. Here we investigated how hRTEL1 contributes to telomere maintenance in human primary as well as tumor cells. Transient depletion of hRTEL1 resulted in rapid telomere shortening only in the context of telomerase-positive cells with very long telomeres and high levels of telomerase. The effect of hRTEL1 on telomere length is telomerase dependent without impacting telomerase biogenesis or targeting of the enzyme to telomeres. Instead, RTEL1 depletion led to a decrease in both G-overhang content and POT1 association with telomeres with limited telomere uncapping. Strikingly, overexpression of POT1 restored telomere length but not the overhang, demonstrating that G-overhang loss is the primary defect caused by RTEL1 depletion. We propose that hRTEL1 contributes to the maintenance of long telomeres by preserving long G-overhangs, thereby facilitating POT1 binding and elongation by telomerase.

UI	MeSH Term	Description	Entries
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004265	DNA Helicases	Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition, DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.	ATP-Dependent DNA Helicase,DNA Helicase,DNA Unwinding Protein,DNA Unwinding Proteins,ATP-Dependent DNA Helicases,DNA Helicase A,DNA Helicase E,DNA Helicase II,DNA Helicase III,ATP Dependent DNA Helicase,ATP Dependent DNA Helicases,DNA Helicase, ATP-Dependent,DNA Helicases, ATP-Dependent,Helicase, ATP-Dependent DNA,Helicase, DNA,Helicases, ATP-Dependent DNA,Helicases, DNA,Protein, DNA Unwinding,Unwinding Protein, DNA,Unwinding Proteins, DNA
D006147	Guanine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000089804	Shelterin Complex	A TELOMERE cap complex consisting of telomere-specific proteins in association with telomeric DNA such as telomeric dsDNA-sDNA junction. They are involved in the protection of chromosome ends and TELOMERASE regulation and play a role in CELLULAR SENESCENCE and ageing-related pathology. In general it consists of six mostly TELOMERE-BINDING PROTEINS (POT1, RAP1, TIN2, TPP1, TRF1, and TRF2).	CST Complex,Ctc1-Stn1-Ten1 Complex,POT1-TPP1 Shelterin Complex,Telomere Cap Complex,Telomere POT1-TPP1 Complex,Telomeric Capping Complex,Telomeric Stn1-Ten1 Capping Complex,Telosome,Capping Complex, Telomeric,Complex, CST,Complex, Ctc1-Stn1-Ten1,Complex, POT1-TPP1 Shelterin,Complex, Shelterin,Complex, Telomere POT1-TPP1,Complex, Telomeric Capping,Ctc1 Stn1 Ten1 Complex,POT1 TPP1 Shelterin Complex,POT1-TPP1 Complex, Telomere,Shelterin Complex, POT1-TPP1,Telomere POT1 TPP1 Complex,Telomeric Stn1 Ten1 Capping Complex,Telosomes
D016615	Telomere	A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.	Telomeres
D059505	Telomere Homeostasis	Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends.	Telomere Length Maintenance,Telomere Lengthening,Homeostasis, Telomere,Length Maintenance, Telomere,Lengthening, Telomere,Maintenance, Telomere Length
D019098	Telomerase	An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.	Telomerase Catalytic Subunit,Telomerase Reverse Transcriptase,Telomerase Reverse Transcriptase Catalytic Subunit,Catalytic Subunit, Telomerase,Reverse Transcriptase, Telomerase,Subunit, Telomerase Catalytic,Transcriptase, Telomerase Reverse
D034501	Telomere-Binding Proteins	Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.	Telomere-Binding Protein,Double-Stranded Telomere-Binding Proteins,Double-Stranded Telomeric Binding Protein,Single-Stranded Telomere-Binding Protein,Single-Stranded Telomere-Binding Proteins,Telomer-Binding Protein, alpha-Subunit,Telomer-Binding Protein, beta-Subunit,Telomere End-Binding Protein (TEBP),Telomere Repeat Binding Factor,Telomere Repeat Binding Factors,Telomere Repeat Binding Proteins,Telomere-Binding Proteins, Double Stranded,Telomere-Binding Proteins, Single-Stranded,alpha-Telomere-Binding Protein,beta-Telomere-Binding Protein,Double Stranded Telomere Binding Proteins,Double Stranded Telomeric Binding Protein,Protein, Telomere-Binding,Single Stranded Telomere Binding Protein,Single Stranded Telomere Binding Proteins,Telomer Binding Protein, alpha Subunit,Telomer Binding Protein, beta Subunit,Telomere Binding Protein,Telomere Binding Proteins,Telomere Binding Proteins, Double Stranded,Telomere Binding Proteins, Single Stranded,Telomere-Binding Protein, Single-Stranded,Telomere-Binding Proteins, Double-Stranded,alpha Telomere Binding Protein,alpha-Subunit Telomer-Binding Protein,beta Telomere Binding Protein,beta-Subunit Telomer-Binding Protein