Publications

Journal Article Ppublish

PubMed: 40560727 DOI: 10.1016/j.celrep.2025.115900

Telomeres stall DNA loop extrusion by condensin.

Cell Rep 44(7):115900

Authors: Brian T Analikwu, Alice Deshayes, Jaco van der Torre, Thomas M Guérin, Allard J Katan, Claire Béneut, Roman Barth, Jamie Phipps, Vittore Scolari, Xavier Veaute, Didier Busso, Karine Dubrana, Stefano Mattarocci, Cees Dekker, Stéphane Marcand

Affiliations

  • Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands.
  • Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France.
  • Institut Curie, PSL Research University, Sorbonne Université, Paris, France.
  • Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France.
  • Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands.
  • Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France.

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.

MeSH

Biological Science Disciplines, Chromatin, Dna, Telomere

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