Human Telomere Repeat Binding Factor TRF1 Replaces TRF2 Bound to Shelterin Core Hub TIN2 when TPP1 Is Absent. 2019

Tomáš Janovič, and Martin Stojaspal, and Pavel Veverka, and Denisa Horáková, and Ctirad Hofr
LifeB, Chromatin Molecular Complexes, CEITEC and Functional Genomics and Proteomics, National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno CZ-62500, Czech Republic.

Human telomeric repeat binding factors TRF1 and TRF2 along with TIN2 form the core of the shelterin complex that protects chromosome ends against unwanted end-joining and DNA repair. We applied a single-molecule approach to assess TRF1-TIN2-TRF2 complex formation in solution at physiological conditions. Fluorescence cross-correlation spectroscopy was used to describe the complex assembly by analyzing how coincident fluctuations of differently labeled TRF1 and TRF2 correlate when they move together through the confocal volume of the microscope. We observed, at the single-molecule level, that TRF1 effectively substitutes TRF2 on TIN2. We assessed also the effect of another telomeric factor TPP1 that recruits telomerase to telomeres. We found that TPP1 upon binding to TIN2 induces changes that expand TIN2 binding capacity, such that TIN2 can accommodate both TRF1 and TRF2 simultaneously. We suggest a molecular model that explains why TPP1 is essential for the stable formation of TRF1-TIN2-TRF2 core complex.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072417 Protein Domains Discrete protein structural units that may fold independently of the rest of the protein and have their own functions. Peptide Domain,Protein Domain,Domain, Peptide,Domain, Protein,Domains, Peptide,Domains, Protein,Peptide Domains
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
D055503 Protein Multimerization The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS. Protein Dimerization,Protein Heteromultimerizaton,Protein Multimer Assembly,Protein Trimerization,Assembly, Protein Multimer,Dimerization, Protein,Heteromultimerizaton, Protein,Heteromultimerizatons, Protein,Multimer Assembly, Protein,Multimerization, Protein,Trimerization, Protein
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

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