Telomerebinding

Telomerebinding refers to the set of proteins and factors that specifically recognize and attach to telomeric DNA, the repetitive sequences at the ends of eukaryotic chromosomes. These proteins protect chromosome ends, regulate telomere length, and coordinate replication and the DNA damage response.

Telomeres consist of short, tandem repeats and a single-stranded 3’ overhang. Telomere-binding proteins bind these sequences and structural features to form protective caps, help form higher-order structures such as t-loops, and prevent inappropriate DNA damage signaling. Binding also influences access of the telomerase enzyme that extends telomeres, thereby contributing to length homeostasis.

In humans and many vertebrates, the main telomere-binding complex is shelterin, which includes TRF1 and TRF2 (which bind double-stranded telomeric DNA), POT1 (which binds the single-stranded overhang), and the linker proteins TIN2, TPP1, and RAP1 that connect the complex and regulate its activities. Shelterin protects telomeres from DNA damage responses and modulates telomerase recruitment.

Yeast and other organisms employ additional or alternative telomere-binding systems. In budding yeast, Rap1 binds double-stranded telomeres and Rif1/Rif2 regulate length, while Cdc13 binds single-stranded telomeric DNA to facilitate C-strand synthesis with the Est1–Est2–Est3 telomerase complex. In many eukaryotes, CST (CTC1–STN1–TEN1) also binds single-stranded telomeric DNA and contributes to replication and C-strand fill-in.

Disruption of telomere-binding proteins can lead to genomic instability, aging phenotypes, or cancer, making these factors a focus of genetic, cellular, and clinical research. Experimental approaches include chromatin immunoprecipitation, DNA-binding assays, and fluorescence localization studies.