Biomaterial Database

POT1 association with TRF2 regulates telomere length. 2009

Megan F Kendellen, and Katharine S Barrientos, and Christopher M Counter

Department of Pharmacology and Cancer Biology, Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.

Deleting the OB folds encoding the telomeric single-stranded DNA (ssDNA)-binding activity of the human telomeric protein POT1 induces significant telomere elongation, suggesting that at least one critical aspect of the regulation of telomere length is disrupted by this POT1(DeltaOB) mutant protein. POT1 is known to associate with two proteins through the protein interaction domain retained in POT1(DeltaOB)-the telomeric double-stranded DNA-binding protein TRF2 and the telomere-associated protein TPP1. We report that introducing a mutation that reduces association of POT1 with TRF2, but not a mutation that reduces the association with TPP1, abrogates the ability of POT1(DeltaOB) to promote telomere elongation. Mechanistically, expression of POT1(DeltaOB) reduced the association of TRF2 with POT1, RAP1, and TIN2; however, of these proteins, only ectopic expression of POT1 suppressed the telomere elongation induced by POT1(DeltaOB). Lastly, replacing endogenous POT1 with a full-length POT1 mutant defective in the association with TRF2 induced telomere elongation. Thus, we conclude that the association of POT1 with both ssDNA and TRF2 is critical for telomere length homeostasis.

UI	MeSH Term	Description	Entries
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
D015815	Cell Adhesion Molecules	Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.	Cell Adhesion Molecule,Intercellular Adhesion Molecule,Intercellular Adhesion Molecules,Leukocyte Adhesion Molecule,Leukocyte Adhesion Molecules,Saccharide-Mediated Cell Adhesion Molecules,Saccharide Mediated Cell Adhesion Molecules,Adhesion Molecule, Cell,Adhesion Molecule, Intercellular,Adhesion Molecule, Leukocyte,Adhesion Molecules, Cell,Adhesion Molecules, Intercellular,Adhesion Molecules, Leukocyte,Molecule, Cell Adhesion,Molecule, Intercellular Adhesion,Molecule, Leukocyte Adhesion,Molecules, Cell Adhesion,Molecules, Intercellular Adhesion,Molecules, Leukocyte Adhesion
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
D020827	rap1 GTP-Binding Proteins	A genetically related subfamily of RAP GTP-BINDING PROTEINS that share homology with RAS PROTEINS. They bind to Ras effectors but do not activate them, therefore they may antagonize the effects of RAS PROTEINS. This enzyme was formerly listed as EC 3.6.1.47.	Krev-1 GTP-Binding Protein,SMG p21A GTP-Binding Protein,rap1A GTP-Binding Protein,smg p21 GTP-Binding Protein,Krev-1 Protein,rap1 GTP-Binding Protein,rap1A Protein,smg p21A Protein,GTP-Binding Protein, Krev-1,GTP-Binding Protein, rap1,GTP-Binding Protein, rap1A,GTP-Binding Proteins, rap1,Krev 1 GTP Binding Protein,Krev 1 Protein,SMG p21A GTP Binding Protein,p21A Protein, smg,rap1 GTP Binding Protein,rap1 GTP Binding Proteins,rap1A GTP Binding Protein,smg p21 GTP Binding Protein
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
D035341	Telomeric Repeat Binding Protein 2	A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.	TRF2 Protein,TERF2 Protein,TRBF2 Protein,Trf2 Gene Product,Gene Products, Trf2,Products, Trf2 Gene,Proteins, TERF2,Proteins, TRBF2,Proteins, TRF2,TERF2 Proteins,TRBF2 Proteins,TRF2 Proteins,Trf2 Gene Products