Neocarzinostatin-induced Rad51 nuclear focus formation is cell cycle regulated and aberrant in AT cells.
DNA double-stranded breaks are the most detrimental form of DNA damage and, if not repaired properly, may lead to an accumulation of chromosomal aberrations and eventually tumorigenesis. Proteins of the Rad51/Rad52 epitasis group are crucial for the recombinational repair of DNA double-stranded breaks, whereas the Rad50/NBS1/Mre11 nuclease complex is involved in both the recombinational and the end-joining repair of DNA double-stranded breaks. Herein, we demonstrate that the chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not NBS1, nuclear focus formation in a cell- cycle-dependent manner. Furthermore, neocarzinostatin-induced Rad51 foci formation revealed a slower kinetic change in AT cells, but not in wild-type or NBS cells. In summary, our results suggest that neocarzinostatin induces Rad51 focus formation through an ATM- and cell-cycle-dependent, but NBS1-independent, pathway.
Department of Obstetrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 807, Republic of China. yuanssf@ms33.hinet.net
Shyng-Shiou F
SS
Yuan
Yuan-Kai
YK
Yang
Hsiao-Wen
HW
Chen
Yueh-Fang
YF
Chung
Hsueh-Ling
HL
Chang
Jinn-Huang
JH
Su
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004790:Enzyme Induction; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis; D051135:Rad51 Recombinase; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D009353:Zinostatin; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; D004253:DNA Nucleotidylexotransferase