shelterincomplex

Shelterin, or the telomere protection complex, is a conserved multi-protein assembly that binds the ends of linear chromosomes to safeguard telomeres from inappropriate DNA damage responses and to regulate telomere maintenance. In humans the core components are TRF1, TRF2, POT1, TIN2, TPP1 (also known as ACD), and RAP1. TRF1 and TRF2 bind double-stranded telomeric DNA, while POT1 binds the single-stranded 3' overhang. TIN2 acts as a central scaffold that links the TRF1-TRF2 arm to the POT1-TPP1 subcomplex and to RAP1, which associates with TRF2.

Functions of shelterin include end protection and the suppression of ATM and ATR signaling at chromosome termini, preventing deleterious end-to-end fusions. The complex promotes the formation of t-loops, structures in which the telomere loopbacks bind to the duplex region to conceal the chromosome end. Shelterin also regulates telomere length by modulating access of telomerase and other processing activities; POT1-TPP1 enhances telomerase processivity and recruitment, while TRF1 and TRF2 participate in overall length homeostasis. In addition, shelterin constrains inappropriate homologous recombination at telomeres.

Regulation of shelterin activity involves cell cycle cues and post-translational modifications that coordinate protective functions with DNA replication and telomere elongation. Disruption of shelterin components or their interactions can lead to telomere dysfunction and has been linked to telomere biology disorders, such as dyskeratosis congenita, as well as to cancer, where altered telomere maintenance influences genome stability. The complex is broadly conserved across vertebrates, with variations in subunit composition and regulation.