Dynamics of Ku80 in living hamster cells with DNA double-strand breaks induced by chemotherapeutic drugs.
A variety of chemotherapeutic drugs, e.g., etoposide and bleomycin, are widely used in clinical practice to treat many types of animal malignancies. In the clinical situation, cellular resistance to chemotherapy is a significant component of tumor treatment failure. A variety of DNA repair factors, e.g., Ku80, might be a key contributor to chemoresistance to anticancer agents. In both cancer and normal cells, Ku80 plays a key role as a sensor of DNA double-strand break (DSB) induced by treatment with some chemotherapeutic drugs. Although the localization and mobility of Ku80 play a key role in regulating the physiological function of Ku80, it is not clear whether those of Ku80 are affected after treatment with chemotherapeutic drugs. We examined the localization and mobility of Ku80 in living hamster cells with or without DSBs, which were induced by treatment with chemotherapeutic drugs. Our data showed that Ku80, in contrast to H2AX, is highly mobile in the nuclei. We found that before and after the induction of DNA damage by treatment with etoposide or bleomycin, a major portion of Ku80 is exchanged by the same kinetics in the nuclei of interphase cells. These results suggest that the mobility of a major portion of Ku80 is not affected by DNA DSBs in order to find other DSBs. In addition, the information would be worthy to develop some new chemotherapeutic drugs to treat many types of animal malignancies.
Koike
Manabu
M
DNA Repair Gene Res., National Institute of Radiological Sciences, Chiba, Japan. m_koike@nirs.go.jp
Koike
Aki
A
Sugasawa
Jun
J
Toyooka
Tatsushi
T
Ibuki
Yuko
Y
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D016466:CHO Cells / Q000166:cytology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae / Q000235:genetics*; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006657:Histones / Q000276:immunology; D007700:Kinetics; D000072200:Ku Autoantigen; D018613:Microscopy, Confocal / Q000379:methods
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D006657:Histones; C485184:enhanced green fluorescent protein; D001761:Bleomycin; D049452:Green Fluorescent Proteins; D005047:Etoposide; D000072200:Ku Autoantigen