Biomolecular Condensation at Telomeres: Mechanisms, Dynamics and Functions

Telomeres are dynamic nucleoprotein structures that protect chromosome ends and maintain genome stability. Recent studies have revealed that telomeres can undergo biomolecular condensation through multivalent interactions among telomeric DNA, shelterin proteins, and telomeric RNAs. In this review, we summarize the molecular mechanisms and biological functions of telomeric phase separation. We discuss the roles of telomeric DNA and shelterin proteins, TERRA mediated RNA protein condensation, and functional condensates associated with replication stress, DNA damage, and alternative lengthening of telomeres. We also highlight the regulatory roles of post translational modifications, particularly phosphorylation and SUMOylation, in controlling condensate formation and dynamics. Finally, we discuss the potential links between telomeric phase separation, telomere homeostasis, cellular senescence, genome stability, and tumorigenesis. These findings provide a new framework for understanding telomere organization and its roles in human disease.