Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing

Nicola Crosetto, Abhishek Mitra, Maria Joao Silva, Magda Bienko, Norbert Dojer, Qi Wang, Elif Karaca, Roberto Chiarle, Magdalena Skrzypczak, Krzysztof Ginalski, Philippe Pasero, Maga Rowicka, Ivan Dikic

Research output: Contribution to journalArticlepeer-review

359 Scopus citations


We present a genome-wide approach to map DNA double-strand breaks (DSBs) at nucleotide resolution by a method we termed BLESS (direct in situ breaks labeling, enrichment on streptavidin and next-generation sequencing). We validated and tested BLESS using human and mouse cells and different DSBs-inducing agents and sequencing platforms. BLESS was able to detect telomere ends, Sce endonuclease-induced DSBs and complex genome-wide DSB landscapes. As a proof of principle, we characterized the genomic landscape of sensitivity to replication stress in human cells, and we identified >2,000 nonuniformly distributed aphidicolin-sensitive regions (ASRs) overrepresented in genes and enriched in satellite repeats. ASRs were also enriched in regions rearranged in human cancers, with many cancer-associated genes exhibiting high sensitivity to replication stress. Our method is suitable for genome-wide mapping of DSBs in various cells and experimental conditions, with a specificity and resolution unachievable by current techniques.

Original languageEnglish (US)
Pages (from-to)361-365
Number of pages5
JournalNature Methods
Issue number4
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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