생명과학회지 (Journal of Life Science)

  • 제13권3호
  • /
  • Pages.241-247
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  • 2003
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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DNA-PK-null 세포주의 adriamycin 처리에 의한 G2/M 세포주기 변화

Enhanced Sensitivity and Long-Term G2/M Arrest in Adriamycin-treated DNA-PK-null Cells are Unrelated to DNA Repair Defects

  • 김충희 (경상대학교 수의과대학 (동물의학연구소)) ;
  • 김종수 (경상대학교 수의과대학 (동물의학연구소)) ;
  • ;
  • 김나리 (인제대학교 의과대학 생리학교실) ;
  • 김의용 (인제대학교 의과대학 생리학교실) ;
  • 한진 (인제대학교 의과대학 생리학교실)
  • Kim, Chung-Hee (College of Veterinary Medicine, Gyeongsang National University (Institute of Animal Medicine)) ;
  • Kim, Jong-Soo (College of Veterinary Medicine, Gyeongsang National University (Institute of Animal Medicine)) ;
  • Van Cuong, Dang (Department of Physiology & Biophysics, College of Medicine, Inje University) ;
  • Kim, Na-Ri (Department of Physiology & Biophysics, College of Medicine, Inje University) ;
  • Kim, Eui-Yong (Department of Physiology & Biophysics, College of Medicine, Inje University) ;
  • Han, Jin (Department of Physiology & Biophysics, College of Medicine, Inje University)
  • 발행 : 2003.06.01
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초록

DNA 손상 유발을 위해 cisplatin, mitomycin 그리고 adriamycin을 농도별로 처리하여 세포독성 효과 및 세포주기 분포를 조사하였다. 이들 약제중 adriamycin의 감수성이 가장 높았으며 특히 $Ku80^{-/-}MEFs$가 현저한 세포독성 감수성 효과를 나타내었다. DNA 회복과 관련된 S phase의 분포도를 알아보기 위하여 adriamycin을 처리한 결과 DNA-$PKcs^{-/-}MEFs$와 $Ku80^{-/-}MEFs$ 모두에서 S phase는 대조군과 비슷하게 나타났다. 그리고 DNA$PKcs^{-/-}MEFs$에 adriamycin 처리시 6시간 경과 후 $G_2$/M phase가 증가되었으나 30시간 경과시 정상으로 회복되었다. 그러나 $Ku80^{-/-}MEFs$는 6시간 경과 이후 36시간 경과시 까지 $G_2$/M phase가 지속적으로 증가하다 결국 사멸되었다. 따라서 Ku80는 세포주기 조절 유전자의 발현을 위해 필수적인 단백질이며 Ku80의 결핍은 $G_2$M phase에서 다음 단계로의 세포주기 변화를 상실하여 사멸하게 된다. 그러므로 $Ku80^{-/-}MEFs$가 대조군과 다른 반응을 나타내는 것은 DNA 회복정도의 차이에서 오는 것이 아니라 세포주기 조절유전자 발현의 차이에서 오는 것으로 사료된다.

While the DNA-protein kinase (DNA-PK) complex, comprised of DNA-PKcs and Ku80, is primary involved in the repair of DNA double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts (MEFs) derived from either wild-type (Wt) or DNA-PKcs-null (DNA-$PKcs^{-/-}$) mice with various stress inducing agents revealed that adriamycin was markedly more cytotoxic for $Ku80^{-/-}MEFs$ and led to their long-term accumulation in the $G_2$/M phase. This differential response was not due to differences in DNA repair, since adrimycin-triggered DNA damage was repaired with comparable efficiency in both Wt and $Ku80^{-/-}MEFs$, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and $G_2$/M-progression are not only dependent on the cell's DNA repair but also may reflect Ku80's influence on additional cellular processes such as gene expression.

키워드

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