Shelterin reduces the accessibility of telomeric overhangs

Sajad Shiekh, Amanda Jack, Ayush Saurabh, Golam Mustafa, Sineth G. Kodikara, Prabesh Gyawali, Mohammed Enamul Hoque, Steve Pressé, Ahmet Yildiz, Hamza Balci

Research output: Contribution to journalArticlepeer-review


Telomeres terminate with a 50-300 bases long single-stranded G-rich overhang, which can be misrecognized as a DNA damage repair site. Shelterin plays critical roles in maintaining and protecting telomere ends by regulating access of various physiological agents to telomeric DNA, but the underlying mechanism is not well understood. Here, we measure how shelterin affects the accessibility of long telomeric overhangs by monitoring transient binding events of a short complementary peptide nucleic acid (PNA) probe using FRET-PAINT in vitro. We observed that the POT1 subunit of shelterin reduces the accessibility of the PNA probe by ∼2.5-fold, indicating that POT1 effectively binds to and protects otherwise exposed telomeric sequences. In comparison, a four-component shelterin stabilizes POT1 binding to the overhang by tethering POT1 to the double-stranded telomeric DNA and reduces the accessibility of telomeric overhangs by ∼5-fold. This enhanced protection suggests shelterin restructures the junction between single and double-stranded telomere, which is otherwise the most accessible part of the telomeric overhang.

Original languageEnglish (US)
Pages (from-to)12885-12895
Number of pages11
JournalNucleic acids research
Issue number22
StatePublished - Dec 9 2022

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'Shelterin reduces the accessibility of telomeric overhangs'. Together they form a unique fingerprint.

Cite this