Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands
Alice Deshayes
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France
Jaco van der Torre
Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands
Thomas M. Guérin
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France
Allard J. Katan
Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands
Claire Béneut
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France
Roman Barth
Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands
Jamie Phipps
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France
Vittore Scolari
Institut Curie, PSL Research University, Sorbonne Université, Paris, France
Xavier Veaute
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France
Didier Busso
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France
Karine Dubrana
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France
Stefano Mattarocci
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France; Corresponding author
Cees Dekker
Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands; Corresponding author
Stéphane Marcand
Université Paris-Saclay, Université Paris-Cité, CEA, Inserm, Institut de Biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France; Corresponding author
Summary: 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.
