Telomere Recognition and Assembly Mechanism of Mammalian Shelterin

Publication date: 3 January 2017
Source:Cell Reports, Volume 18, Issue 1
Author(s): Fabian Erdel, Katja Kratz, Smaranda Willcox, Jack D. Griffith, Eric C. Greene, Titia de Lange
Shelterin is a six-subunit protein complex that plays crucial roles in telomere length regulation, protection, and maintenance. Although several shelterin subunits have been studied in vitro, the biochemical properties of the fully assembled shelterin complex are not well defined. Here, we characterize shelterin using ensemble biochemical methods, electron microscopy, and single-molecule imaging to determine how shelterin recognizes and assembles onto telomeric repeats. We show that shelterin complexes can exist in solution and primarily locate telomeric DNA through a three-dimensional diffusive search. Shelterin can diffuse along non-telomeric DNA but is impeded by nucleosomes, arguing against extensive one-dimensional diffusion as a viable assembly mechanism. Our work supports a model in which individual shelterin complexes rapidly bind to telomeric repeats as independent functional units, which do not alter the DNA-binding mode of neighboring complexes but, rather, occupy telomeric DNA in a “beads on a string” configuration.

Graphical abstract

Teaser

The shelterin complex safeguards mammalian telomeres. Erdel et al. purify the full shelterin complex and visualize how individual complexes interact with DNA. They find that preassembled shelterin complexes can exist in solution and can rapidly find telomeric repeats by three-dimensional diffusion to ensure efficient and persistent telomere protection.


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