Telomeres stall DNA loop extrusion by condensin

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.

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Publication Details

Journal
Cell Reports
Published
2025-06-24
DOI
https://doi.org/10.1016/j.celrep.2025.115900
Citations
5
Primary Topic
DNA and Nucleic Acid Chemistry
Type
article
Field-Weighted Citation Impact
4.03
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Telomeres stall DNA loop extrusion by condensin

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Telomeres stall DNA loop extrusion by condensin

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article en
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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.

Cell ReportsVol. 44(7)
Inserm (FR), Université Paris Cité (FR), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), Université Paris Sciences et Lettres (FR), Université Paris-Saclay (FR), Sorbonne Université (FR), CEA Paris-Saclay (FR), Institut de Radiobiologie Cellulaire et Moléculaire (FR), Institut Curie (FR), Delft University of Technology (NL)
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Openalex Percentile: Top 6%
DNA and Nucleic Acid Chemistry
4.03
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