Reid R J, Benedetti P, Bjornsti M A
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, 233 S. 10th St., Philadelphia, PA 19107, USA.
Biochim Biophys Acta. 1998 Oct 1;1400(1-3):289-300. doi: 10.1016/s0167-4781(98)00142-0.
The budding yeast Saccharomyces cerevisiae has been exploited to investigate the cytotoxic mechanisms of drugs that target DNA topoisomerases. This model organism has been used to establish eukaryotic DNA topoisomerase I or II as the cellular target of specific antineoplastic agents, to define mutations in these enzymes that confer drug resistance and to elucidate the cellular factors that modulate cell sensitivity to DNA topoisomerase-targeted drugs. These findings have provided valuable insights into the critical activities of these enzymes and how perturbing their functions produces DNA damage and cell death.
芽殖酵母酿酒酵母已被用于研究靶向DNA拓扑异构酶的药物的细胞毒性机制。这种模式生物已被用于确定真核DNA拓扑异构酶I或II为特定抗肿瘤药物的细胞靶点,确定这些酶中赋予耐药性的突变,并阐明调节细胞对DNA拓扑异构酶靶向药物敏感性的细胞因子。这些发现为这些酶的关键活性以及干扰其功能如何导致DNA损伤和细胞死亡提供了有价值的见解。