Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells

Huifen Cao, Lorena Salazar-García, Fan Gao, Thor Wahlestedt, Chun Lin Wu, Xueer Han, Ye Cai, Dongyang Xu, Fang Wang, Lu Tang, Natalie Ricciardi, Ding Ding Cai, Huifang Wang, Mario P.S. Chin, James A. Timmons, Claes Wahlestedt, Philipp Kapranov

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number5799
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Cao, H., Salazar-García, L., Gao, F., Wahlestedt, T., Wu, C. L., Han, X., Cai, Y., Xu, D., Wang, F., Tang, L., Ricciardi, N., Cai, D. D., Wang, H., Chin, M. P. S., Timmons, J. A., Wahlestedt, C., & Kapranov, P. (2019). Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells. Nature communications, 10(1), [5799]. https://doi.org/10.1038/s41467-019-13602-7