2025/02/10 by Federico Teloni, Zsuzsanna Takács, Michael Mitter +6 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genomics and Chromatin Dynamics #Bacterial Genetics and Biotechnology #RNA and protein synthesis mechanisms
paper · doi:10.1101/2025.02.10.637359
openalex publication_date 2025/02/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
Accurate repair of DNA double-strand breaks (DSBs) is essential for genome stability, and defective repair underlies diseases such as cancer. Homologous recombination uses an intact homologous sequence to faithfully restore damaged DNA, yet how broken DNA ends find homologous sites in a genome containing billions of non-homologous bases remains unclear. Here, we introduce sister-pore-C, a high-resolution method for mapping intra- and trans-molecular interactions in replicated chromosomes. We show that DSBs reshape chromosome architecture by recruiting two functionally distinct pools of cohesin. Loop-forming cohesin accumulates across a megabase-scale domain to control homology sampling within topologically associating domains (TADs) surrounding the break site, while cohesive cohesin concentrates at the break site to tether broken ends to the sister chromatid. This dual mechanism restricts the homology search space, highlighting how chromosome conformation helps preserve genomic integrity.