Abstract
AbstractAccurate repair of DNA damage is critical for maintenance of genomic integrity and cellular survival. Because damage occurs non-uniformly across the genome, single-cell resolution is required for proper interrogation, but sensitive detection has remained challenging. Here, we present genome-wide binding profiles of DNA double-strand break repair proteins in single cells, allowing for the study of heterogeneity in genomic damage locations and associated repair features. By unbiasedly detecting repair-enriched segments, we find that repair proteins often occupy entire topologically associating domains and mimic variability in chromatin loop anchoring. Genomic loci that form damage-specific 3D contacts show multi-way repair coordination in individual cells that becomes stronger according to the number of interaction partners. These findings advance our understanding of genome stability in the context of nuclear organization.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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