Telomeres stall DNA loop extrusion by condensin

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 cond...

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Main 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
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725006710
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Summary: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.
ISSN:2211-1247