Grossmann K F, Brown J C, Moses R E
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
Mutat Res. 1999 May 14;434(1):29-39. doi: 10.1016/s0921-8777(99)00011-7.
Cisplatin (CDDP) has been used as a DNA cross-linking agent to evaluate whether there is a specific cell cycle checkpoint response to such damage in Saccharomyces cerevisiae (S. cerevisiae). Fluorescent-activated cell sorting (FACS) analysis showed only a G2/M checkpoint, normal exit from G1 and progression through S-phase following alpha-factor arrest and CDDP treatment. Of the checkpoint mutants tested, rad9, rad17 and rad24, did not show increased sensitivity to CDDP compared to isogenic wild-type cells. However, other checkpoint mutants tested (mec1, mec3 and rad53) showed increased sensitivity to CDDP, as did controls with a defect in excision repair (rad1 and rad14) or a defect in recombination (rad51 and rad52). Thus, by survival and cell cycle kinetics, it appears that DNA cross-links do not inhibit entry into S-phase or slow DNA replication and that replication continues after cisplatin treatment in yeast.
顺铂（CDDP）已被用作一种DNA交联剂，以评估酿酒酵母（S. cerevisiae）中是否存在针对此类损伤的特定细胞周期检查点反应。荧光激活细胞分选（FACS）分析表明，在α因子阻滞和CDDP处理后，仅存在G2/M检查点，细胞从G1期正常退出并通过S期进展。在所测试的检查点突变体中，rad9、rad17和rad24与同基因野生型细胞相比，对CDDP并未表现出更高的敏感性。然而，所测试的其他检查点突变体（mec1、mec3和rad53）对CDDP表现出更高的敏感性，具有切除修复缺陷（rad1和rad14）或重组缺陷（rad51和rad52）的对照也是如此。因此，通过存活率和细胞周期动力学分析，似乎DNA交联并不抑制进入S期或减缓DNA复制，并且在酵母中顺铂处理后复制仍会继续。
