Finding DNA Ends within a Haystack of Chromatin
| Autor: | Ujjwal Banerjee, Evi Soutoglou |
|---|---|
| Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Peney, Maité |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
genetic processes Genomics Computational biology Biology [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Genome Article 03 medical and health sciences chemistry.chemical_compound Humans Molecular Biology Genetics Chromosome Fragile Sites Chromosomal fragile site fungi food and beverages [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology DNA Cell Biology Chromatin enzymes and coenzymes (carbohydrates) 030104 developmental biology chemistry Chromosome Fragile Site Dna breaks biological phenomena cell phenomena and immunity Haystack |
| Zdroj: | Molecular Cell Molecular Cell, Elsevier, 2016, 63 (5), pp.726-728. ⟨10.1016/j.molcel.2016.08.012⟩ Molecular Cell, 2016, 63 (5), pp.726-728. ⟨10.1016/j.molcel.2016.08.012⟩ |
| ISSN: | 1097-2765 1097-4164 |
| DOI: | 10.1016/j.molcel.2016.08.012 |
| Popis: | DNA double-strand breaks (DSBs) arise during physiological transcription, DNA replication, and antigen receptor diversification. Mistargeting or misprocessing of DSBs can result in pathological structural variation and mutation. Here we describe a sensitive method (END-seq) to monitor DNA end resection and DSBs genome-wide at base-pair resolution in vivo. We utilized END-seq to determine the frequency and spectrum of restriction-enzyme-, zinc-finger-nuclease-, and RAG-induced DSBs. Beyond sequence preference, chromatin features dictate the repertoire of these genome-modifying enzymes. END-seq can detect at least one DSB per cell among 10,000 cells not harboring DSBs, and we estimate that up to one out of 60 cells contains off-target RAG cleavage. In addition to site-specific cleavage, we detect DSBs distributed over extended regions during immunoglobulin class-switch recombination. Thus, END-seq provides a snapshot of DNA ends genome-wide, which can be utilized for understanding genome-editing specificities and the influence of chromatin on DSB pathway choice. |
| Databáze: | OpenAIRE |
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