Yuan Shyng-Shiou F, Yang Yuan-Kai, Chen Hsiao-Wen, Chung Yueh-Fang, Chang Hsueh-Ling, Su Jinn-Huang
Department of Obstetrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 807, Republic of China.
Toxicol Appl Pharmacol. 2003 Nov 1;192(3):231-6. doi: 10.1016/s0041-008x(03)00013-9.
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.
DNA双链断裂是最具危害性的DNA损伤形式，若不能得到正确修复，可能导致染色体畸变的积累并最终引发肿瘤形成。Rad51/Rad52上位作用组的蛋白质对于DNA双链断裂的重组修复至关重要，而Rad50/NBS1/Mre11核酸酶复合体则参与DNA双链断裂的重组修复和末端连接修复。在此，我们证明化疗烯二炔类抗生素新制癌菌素以细胞周期依赖性方式诱导Rad51而非NBS1形成核集落。此外，新制癌菌素诱导的Rad51集落形成在AT细胞中显示出较慢的动力学变化，但在野生型或NBS细胞中则不然。总之，我们的结果表明新制癌菌素通过一条依赖于ATM和细胞周期但不依赖于NBS1的途径诱导Rad51集落形成。
