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

DNA-PK-null 세포주의 adriamycin 처리에 의한 G2/M 세포주기 변화

  • 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)
  • 김충희 (경상대학교 수의과대학 (동물의학연구소)) ;
  • 김종수 (경상대학교 수의과대학 (동물의학연구소)) ;
  • ;
  • 김나리 (인제대학교 의과대학 생리학교실) ;
  • 김의용 (인제대학교 의과대학 생리학교실) ;
  • 한진 (인제대학교 의과대학 생리학교실)
  • Published : 2003.06.01

Abstract

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.

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