Structure and biophysical studies of telomeric G-overhang

Telomeres are protective caps at chromosome ends, comprised of repetitive DNA sequences. Their single-stranded G-overhang is key to stability, with POT1 binding this region to prevent erroneous DNA repair. Despite its significance, the G-overhang’s detailed structure was unclear. Using chemical cross-linking mass spectrometry and cryo-electron microscopy, we uncovered its higher-order organisation. POT1 forms a dimeric core particle to package single stranded telomeric DNA for end protection. Several disease-related POT1 mutations occur at this dimer interface, highlighting its importance for genome stability. These findings advance understanding of telomere structure and mechanisms safeguarding chromosome ends. Furthermore, this research could improve cancer treatments in the future