Telomere Recognition and Assembly Mechanism of Mammalian Shelterin.

Abstract:

: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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Erdel F,Kratz K,Willcox S,Griffith JD,Greene EC,de Lange T

doi

10.1016/j.celrep.2016.12.005

subject

Has Abstract

pub_date

2017-01-03 00:00:00

pages

41-53

issue

1

issn

2211-1247

pii

S2211-1247(16)31678-3

journal_volume

18

pub_type

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