University of Minnesota Medical School, Duluth Campus, Duluth, MN, 55805, USA.
Anticancer Res. 2013 May;33(5):2037-41.
Thymidine deprivation is a common cancer treatment. This study examines the role of replication arrest and uracil DNA repair in response to thymidine deprivation.
Strains of S. cerevisiae deficient in various replication and DNA repair functions were tested for sensitivity to thymidine deprivation induced by the antifolate aminopterin. Cell survival and DNA content were assayed following drug treatment.
Most arrest mutants were more sensitive to aminopterin than was the parental strain. Inactivation of uracil glycosylase in arrest mutants led to a partial reduction in toxicity for some double-mutants. DNA content during exposure to aminopterin was similar in parental and single mutants. However, cells deficient in both arrest and uracil glycosylase functions exhibited continued DNA synthesis, suggesting that uracil glycosylase activity contributes to replication arrest during thymidine deprivation.
Replication arrest and uracil DNA repair are important and overlapping determinants of cellular response to thymidine deprivation.
胸苷剥夺是一种常见的癌症治疗方法。本研究探讨了复制停滞和尿嘧啶 DNA 修复在应对胸苷剥夺中的作用。
检测了各种复制和 DNA 修复功能缺陷的酿酒酵母菌株对叶酸类似物氨基喋呤诱导的胸苷剥夺的敏感性。药物处理后检测细胞存活率和 DNA 含量。
大多数停滞突变体比亲本菌株对氨基喋呤更敏感。在停滞突变体中失活尿嘧啶糖苷酶会导致一些双突变体的毒性部分降低。在暴露于氨基喋呤期间，亲本和单突变体的 DNA 含量相似。然而，同时缺乏停滞和尿嘧啶糖苷酶功能的细胞表现出持续的 DNA 合成，表明尿嘧啶糖苷酶活性有助于胸苷剥夺期间的复制停滞。
复制停滞和尿嘧啶 DNA 修复是细胞对胸苷剥夺反应的重要且重叠的决定因素。
