Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 12 2019
20 12 2019
Historique:
received:
23
07
2019
accepted:
11
11
2019
entrez:
22
12
2019
pubmed:
22
12
2019
medline:
9
4
2020
Statut:
epublish
Résumé
Single-strand breaks (SSBs) represent the major form of DNA damage, yet techniques to map these lesions genome-wide with nucleotide-level precision are limited. Here, we present a method, termed SSiNGLe, and demonstrate its utility to explore the distribution and dynamic changes in genome-wide SSBs in response to different biological and environmental stimuli. We validate SSiNGLe using two very distinct sequencing techniques and apply it to derive global profiles of SSBs in different biological states. Strikingly, we show that patterns of SSBs in the genome are non-random, specific to different biological states, enriched in regulatory elements, exons, introns, specific types of repeats and exhibit differential preference for the template strand between exons and introns. Furthermore, we show that breaks likely contribute to naturally occurring sequence variants. Finally, we demonstrate strong links between SSB patterns and age. Overall, SSiNGLe provides access to unexplored realms of cellular biology, not obtainable with current approaches.
Identifiants
pubmed: 31862872
doi: 10.1038/s41467-019-13602-7
pii: 10.1038/s41467-019-13602-7
pmc: PMC6925131
doi:
Substances chimiques
DNA, Single-Stranded
0
Nucleotides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
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