Pot1

Pot1, short for Protection of Telomeres 1, is a telomere-binding protein that protects chromosome ends and helps regulate telomere maintenance. It binds to the single-stranded G-rich telomeric DNA overhangs, commonly through OB-fold domains, and is a core component of the shelterin complex in many eukaryotes. By occupying the telomeric overhang, Pot1 prevents inappropriate activation of DNA damage responses, particularly ATR signaling, which can arise at exposed chromosome ends. This end protection supports genome stability and proper telomere replication.

In humans, POT1 forms a functional unit with TPP1; together they associate with shelterin components such as TRF1, TRF2, TIN2, and RAP1 to regulate telomere structure and function. The POT1-TPP1 subcomplex influences telomerase access and processivity, influencing telomere length homeostasis. POT1’s activity is modulated by cellular context and cell cycle cues, and it interacts with other shelterin factors to anchor telomeres to the nuclear architecture.

In budding and fission yeast, Pot1 orthologs bind telomeric repeats and participate in a conserved network with other telomere regulators to protect ends and modulate telomerase activity, though the specific regulatory interactions vary by species.

Clinical relevance: Germline POT1 mutations have been linked to increased risk of certain cancers, including melanoma and glioma, often through altered telomere length maintenance or telomere protection. Dysregulation of Pot1 function can contribute to telomere biology disorders characterized by abnormal telomere length dynamics.

See also: shelterin, telomere, telomerase, OB-fold, telomere biology disorders.