Cell reportsAug 24, 2025

TRF1 and TRF2 create separate protective groups at chromosome ends

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

Shelterin proteins were found to be present at telomeres in equal numbers.

The shelterin complex is composed of six proteins that play a role in protecting chromosome ends from DNA repair.
Distinct subcomplexes of shelterin, specifically TRF1-TIN2-TPP1-POT1 and TRF2-RAP1, bind to different sites on telomeres.
TRF1-TIN2-TPP1-POT1 associates tightly with telomeres, while TRF2-RAP1 binds more dynamically.
The dynamic binding of TRF2-RAP1 may facilitate the recruitment of protective co-factors at chromosome ends.
This research provides insights into the function of shelterin in telomere maintenance and chromatin structure.

Simplified

The shelterin complex protects chromosome ends from aberrant DNA repair and regulates telomerase access to telomeres. Shelterin is composed of six proteins (TRF1, TRF2, TIN2, TPP1, POT1, and RAP1) that can assemble into various subcomplexes in vitro, but their stoichiometry and dynamics in cells remain poorly understood. To quantitatively analyze shelterin function, we generated a panel of human cancer cell lines expressing HaloTagged shelterin proteins from their endogenous loci. We determined both the total and telomeric abundance of each subunit, demonstrating that shelterin proteins are present at telomeres in equal numbers. Using single-molecule live-cell imaging, we showed that TRF1-TIN2-TPP1-POT1 and TRF2-RAP1 form distinct subcomplexes that bind non-overlapping sites on telomeric chromatin. TRF1-TIN2-TPP1-POT1 tightly associates with telomeres, whereas TRF2-RAP1 binds more dynamically, facilitating the recruitment of co-factors that protect chromosome ends. Altogether, our work provides mechanistic insight into shelterin function in telomere maintenance and advances our understanding of telomeric chromatin architecture.