Next-generation sequencing of apoptotic DNA breakpoints reveals association with actively transcribed genes and gene translocations.
Journal Article (Journal Article)
DNA fragmentation is a well-recognized hallmark of apoptosis. However, the precise DNA sequences cleaved during apoptosis triggered by distinct mechanisms remain unclear. We used next-generation sequencing of DNA fragments generated in Actinomycin D-treated human HL-60 leukemic cells to generate a high-throughput, global map of apoptotic DNA breakpoints. These data highlighted that DNA breaks are non-random and show a significant association with active genes and open chromatin regions. We noted that transcription factor binding sites were also enriched within a fraction of the apoptotic breakpoints. Interestingly, extensive apoptotic cleavage was noted within genes that are frequently translocated in human cancers. We speculate that the non-random fragmentation of DNA during apoptosis may contribute to gene translocations and the development of human cancers.
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Duke Authors
Cited Authors
- Fullwood, MJ; Lee, J; Lin, L; Li, G; Huss, M; Ng, P; Sung, W-K; Shenolikar, S
Published Date
- 2011
Published In
Volume / Issue
- 6 / 11
Start / End Page
- e26054 -
PubMed ID
- 22087219
Pubmed Central ID
- PMC3210745
Electronic International Standard Serial Number (EISSN)
- 1932-6203
Digital Object Identifier (DOI)
- 10.1371/journal.pone.0026054
Language
- eng
Conference Location
- United States