Next-generation sequencing of apoptotic DNA breakpoints reveals association with actively transcribed genes and gene translocations.

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.

Full Text

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

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0026054

Language

  • eng

Conference Location

  • United States