Comparison of Different Methods to Determine the DNA Sequence Preference of Ionising Radiation-Induced DNA Damage

Genes (Basel). 2019 Dec 20;11(1):8. doi: 10.3390/genes11010008.

Abstract

Ionising radiation (IR) is known to induce a wide variety of lesions in DNA. In this review, we compared three different techniques that examined the DNA sequence preference of IR-induced DNA damage at nucleotide resolution. These three techniques were: the linear amplification/polymerase stop assay, the end-labelling procedure, and Illumina next-generation genome-wide sequencing. The DNA sequence preference of IR-induced DNA damage was compared in purified DNA sequences including human genomic DNA. It was found that the DNA sequence preference of IR-induced DNA damage identified by the end-labelling procedure (that mainly detected single-strand breaks) and Illumina next-generation genome-wide sequencing (that mainly detected double-strand breaks) was at C nucleotides, while the linear amplification/polymerase stop assay (that mainly detected base damage) was at G nucleotides. A consensus sequence at the IR-induced DNA damage was found to be 5'-AGGC*C for the end-labelling technique, 5'-GGC*MH (where * is the cleavage site, M is A or C, H is any nucleotide except G) for the genome-wide technique, and 5'-GG* for the linear amplification/polymerase stop procedure. These three different approaches are important because they provide a deeper insight into the mechanism of action of IR-induced DNA damage.

Keywords: DNA damage; DNA sequence preference; fluorescently end-labelled DNA; gamma radiation; genome-wide sequencing; polymerase stop assay.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA Damage*
  • Genome, Human / radiation effects*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / radiation effects
  • Radiation, Ionizing
  • Sequence Analysis, DNA