Cell lines derived from a Medaka radiation-sensitive mutant have defects in DNA double-strand break responses

Masayuki Hidaka, Shoji Oda, Yoshikazu Kuwahara, Manabu Fukumoto, Hiroshi Mitani

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

It was reported that the radiation-sensitive Medaka mutant "ric1" has a defect in the repair of DNA double-strand breaks (DSBs) induced by γ-rays during early embryogenesis. To study the cellular response of a ric1 mutant to ionizing radiation (IR), we established the mutant embryonic cell lines RIC1-e9, RIC1- e42, RIC1-e43. Following exposure to γ-irradiation, the DSBs in wild-type cells were repaired within 1 h, while those in RIC1 cells were not rejoined even after 2 h. Cell death was induced in the wild-type cells with cell fragmentation, but only a small proportion of the RIC1 cells underwent cell death, and without cell fragmentation. Although both wild-type and RIC1 cells showed mitotic inhibition immediately after γ- irradiation, cell division was much slower to resume in the wild-type cells (20 h versus 12 h). In both wild-type and RIC1 cells, Ser139 phosphorylated H2AX (γH2AX) foci were formed after γ-irradiation, however, the γH2AX foci disappeared more quickly in the RIC1 cell lines. These results suggest that the instability of γH2AX foci in RIC1 cells cause an aberration of the DNA damage response. As RIC1 cultured cells showed similar defective DNA repair as ric1 embryos and RIC1 cells revealed defective cell death and cell cycle checkpoint, they are useful for investigating DNA damage responses in vitro.

Original languageEnglish
Pages (from-to)165-171
Number of pages7
JournalJournal of radiation research
Volume51
Issue number2
DOIs
Publication statusPublished - 2010 Mar 25

Keywords

  • Apoptosis
  • Cell cycle checkpoint
  • DNA repair
  • Medaka
  • γH2AX

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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