Telomeres stall DNA loop extrusion by condensin

Journal Article (2025)
Author(s)

Brian T. Analikwu (TU Delft - Applied Sciences, Kavli institute of nanoscience Delft)

Alice Deshayes (Université Paris Cité, Institut François Jacob, CEA, Inserm, Université Paris-Saclay, Paris)

Jaco van der Torre (TU Delft - Applied Sciences, Kavli institute of nanoscience Delft)

Thomas M. Guérin (Université Paris Cité, Inserm, Université Paris-Saclay, Paris, CEA, Institut François Jacob)

Allard J. Katan (Kavli institute of nanoscience Delft, TU Delft - Applied Sciences)

Roman Barth (Kavli institute of nanoscience Delft, TU Delft - Applied Sciences)

Stefano Mattarocci (Université Paris-Saclay, Paris, Inserm, Institut François Jacob, CEA, Université Paris Cité)

Cees Dekker (TU Delft - Applied Sciences, Kavli institute of nanoscience Delft)

Stéphane Marcand (CEA, Université Paris Cité, Inserm, Institut François Jacob, Université Paris-Saclay, Paris)

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Research Group
BN/Cees Dekker Lab
DOI related publication
https://doi.org/10.1016/j.celrep.2025.115900 Final published version
More Info
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Publication Year
2025
Language
English
Research Group
BN/Cees Dekker Lab
Journal title
Cell Reports
Issue number
7
Volume number
44
Article number
115900
Downloads counter
323
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Abstract

DNA loop extrusion by SMC proteins is a key process underlying chromosomal organization. It is unknown how loop extruders interact with telomeres where DNA is densely covered with proteins. Using complementary in vivo and in vitro single-molecule approaches, we study how loop-extruding condensin interacts with Rap1, the telomeric DNA-binding protein of Saccharomyces cerevisiae. We show that dense linear Rap1 arrays can completely halt DNA loop extrusion, with a blocking efficiency depending on the array length and the DNA gap size between proteins. In anaphase cells, dense Rap1 arrays are found to accumulate condensin and to cause a local chromatin decompaction, as monitored with a microscopy-based approach, with direct implications for the resolution of dicentric chromosomes produced by telomere fusions. Our findings show that linear arrays of DNA-bound proteins can efficiently halt DNA loop extrusion by SMC proteins, which may impact cellular processes from telomere functions to transcription and DNA repair.