Development of a high-content screening method for chemicals modulating DNA damage response

Sunshin Kim, Dong Hwa Jun, Hye Jin Kim, Kyung Chae Jeong, Chang Hun Lee

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The cellular response to DNA damage is emerging as a promising target for cancer therapy. In the present study, the authors exploited the relationship between the level of the phosphorylated form of histone H2AX (γH2AX) and the extent of DNA damage and developed a quantitative, cell-based, high-content screening system for measuring the DNA damage response (DDR). In this system, the authors quantified the level of γH2AX by measuring DNA damage-induced γH2AX nuclear foci using an automated cell imager. They found that the total area of γH2AX foci per cell exhibited a good correlation with the concentration of DNA damage-inducing agents, including etoposide. The effects of 2 well-known inhibitors of DNA damage could be quantified using this system, suggesting the suitability of the γH2AX-foci quantification method for large-scale screening applications. This was confirmed by using this method to screen a chemical library; the resulting "hits" included compounds that inhibited early signaling events in DDR, as well those that inhibited subsequent DNA damage repair processes. Overall, this γH2AX foci-measuring system may be an effective screening method for identifying DNA damage response inhibitors that could eventually be used to develop novel anticancer drugs.

Original languageEnglish
Pages (from-to)259-265
Number of pages7
JournalJournal of Biomolecular Screening
Volume16
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • cancer therapy
  • cell-based high-content screening
  • DNA damage response
  • phosphorylated histone H2 variant (γH2AX)

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