Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells
| Autor: | Fang Wang, James A. Timmons, Xueer Han, Lu Tang, Claes Wahlestedt, Chun Lin Wu, Mario P.S. Chin, Huifen Cao, Fan Gao, Ye Cai, Dongyang Xu, Lorena Salazar-García, Philipp Kapranov, Thor Wahlestedt, Natalie R. Ricciardi, Huifang Wang, Ding Ding Cai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DNA damage Science DNA Single-Stranded General Physics and Astronomy Computational biology Biology Genome Article General Biochemistry Genetics and Molecular Biology Genomic analysis Mice 03 medical and health sciences chemistry.chemical_compound Exon 0302 clinical medicine Animals Humans DNA Breaks Single-Stranded lcsh:Science Cellular Senescence Sequence (medicine) Multidisciplinary Genome Human Nucleotides DNA damage and repair Intron Exons Genomics General Chemistry Introns Human genetics 030104 developmental biology chemistry Coding strand lcsh:Q K562 Cells Software 030217 neurology & neurosurgery DNA HeLa Cells |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-13602-7 |
| Popis: | 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. Single strand breaks represent the most common form of DNA damage yet no methods to map them in a genome-wide fashion at single nucleotide resolution exist. Here the authors develop such a method and apply to uncover patterns of single-strand DNA “breakome” in different biological conditions. |
| Databáze: | OpenAIRE |
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