Search
Search results for: TRF2
-
TRF1 and TRF2: pioneering targets in telomere-based cancer therapy
PublicationThis article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often...
-
Molecular basis and quantitative assessment of TRF1 and TRF2 protein interactions with TIN2 and Apollo peptides
PublicationShelterin is a six-protein complex (TRF1, TRF2, POT1, RAP1, TIN2, and TPP1) that also functions in smaller subsets in regulation and protection of human telomeres. Two closely related proteins, TRF1 and TRF2, make high-affinity contact directly with double-stranded telomeric DNA and serve as a molecular platform. Protein TIN2 binds to TRF1 and TRF2 dimer-forming domains, whereas Apollo makes interaction only with TRF2. To elucidate...
-
The structurally similar TRFH domain of TRF1 and TRF2 dimers shows distinct behaviour towards TIN2
PublicationThe telomere repeat binding-factor 1 and 2 (TRF1 and TRF2) proteins of the shelterin complex bind to duplex telomeric DNA as homodimers, and the homodimerization is mediated by their TRFH (TRF-homology) domains. We performed molecular dynamic (MD) simulations of the dimer forms of TRF1TRFH and TRF2TRFH in the presence/absence of the TIN2TBM (TIN2, TRF-interacting nuclear protein 2, TBM, TRF-binding motif) peptide. The MD results...
-
Evaluation and cellular responses of modulators of TRF1/TRF2 protein’s function as potential anticancer drugs interfering with telomeric shelterin’s function
PublicationA number of proteins that interact with telomeres have been identified in human cells, indicating the high plasticity of human nucleoprotein complex organization. The most important complex is the "shelterin" complex, which consists of six proteins: TRF1, TRF2, TIN2, POT1, TPP1. The TRF1 and TRF2 directly bind to telomeric double-stranded DNA and the TIN2 protein. The TIN2 protein also binds to the TPP1 protein, stabilizing the...
-
Compounds modulating function of telomeric proteins TRF1 and TRF2
ProjectsProject realized in Department of Pharmaceutical Technology and Biochemistry
-
Molecular Recognition in Complexes of TRF Proteins with Telomeric DNA
PublicationTelomeres are specialized nucleoprotein assemblies that protect the ends of linear chromosomes. In humans and many other species, telomeres consist of tandem TTAGGG repeats bound by a protein complex known as shelterin that remodels telomeric DNA into a protective loop structure and regulates telomere homeostasis. Shelterin recognizes telomeric repeats through its two major components known as Telomere Repeat-Binding Factors, TRF1...
-
Confocal microscopy analysis of DNA DSB in telomerase negative cells after exposure to TXT2 and TXT4
Open Research DataThe data sets contain confocal microscopic images showing the γ-H2AX with TRF2 after treatment of NHBE and U2OS cell lines with TXT2 and TXT4 in equitoxic concentrations. Images were acquired with an LSM 800 inverted laser scanning confocal microscope (Carl Zeiss; Dresden, Germany) equipped with an Airyscan detector using a ×63 1.4 NA Plan Apochromat...
-
Analysis of induction of DNA DSBs on telomeres in A549 cells
Open Research DataData consist of an analysis of DNA DSBs on telomeres. A549 were treated with compounds (TXT4, MTX, DMSO) at IC90 concentration for the indicated time. Images were acquired with an LSM 800 inverted laser scanning confocal microscope (Carl Zeiss; Dresden, Germany) equipped with an Airyscan detector using a ×63 1.4 NA Plan Apochromat objective (Carl Zeiss)....
-
Novel anticancer strategy aimed at targeting shelterin complexes by the induction of structural changes in telomeric DNA: hitting two birds with one stone.
PublicationThe ends of chromosomes in mammals are composed of telomeric DNA containing TTAGGG repeats, which bind specific proteins called shelterins. This telomeric DNA together with shelterins form a cap that protects the ends of chromosomes from being recognized as sites of DNA damage and from chromosomal fusions. Many very successful antitumor drugs used in the treatment of cancer patients bind to DNA, some of them with a prominent sequence...