POT1 mutations cause differential effects on telomere length leading to opposing disease phenotypes.

Abstract

The protection of telomereprotein (POT1) is a telomere-binding protein and is an essential component of the six-memberedshelterin complex, which is associated with the telomeres. POT1 directly binds to the3' single-stranded telomeric overhang and prevents the activation of DNA damage response at telomeres thus preventing the telomere-telomere fusions and genomic instability. POT1 also plays a pivotal role in maintaining telomere length by regulating telomerase-mediated telomere elongation. Mutations in POT1 proteins resultin three different telomere phenotypes, which include long, short, or aberrant telomere length. Long telomeres predispose individuals to cancer, while short or aberrant telomere phenotypes result in pro-aging diseases referred to as telomeropathies. Here, we review the function of POT1 proteins in telomere length hemostasis and how the spectrum of mutations reported in POT1 can be segregated towarddeveloping very distinct diseasephenotypes of cancer and telomeropathies.