在DNA合成停滞的细胞中，胸苷酸合成酶的抑制并非由于复制酶复合物中的变构相互作用。

Thymidylate synthase inhibition in cells with arrested DNA synthesis is not due to an allosteric interaction in the replitase complex.

作者信息

Rode W, Jastreboff M M, Bertino J R

出版信息

Biochem Biophys Res Commun. 1985 Apr 16;128(1):345-51. doi: 10.1016/0006-291x(85)91685-7.

Abstract

Activity of thymidylate synthase was measured in situ in leukemia cells by tritium release from [5-3H]dUrd. Aphidicolin, an inhibitor of DNA polymerase alpha, but not thymidylate synthase, caused a time dependent inhibition of the enzyme when added to the cells after [5-3H]dUrd. Cells treated with hydroxyurea and aphidicolin in sequence before addition of [5-3H]dUrd had a high initial thymidylate synthase activity that decreased with time. This pattern indicates that thymidylate synthase activity is linked to DNA synthesis; however, its inhibition by drugs that inhibit DNA synthesis may be due to accumulation of thymidine nucleotide(s), rather than to an allosteric interaction in the replitase complex.

摘要

通过[5-³H]脱氧尿苷释放的氚来原位测量白血病细胞中胸苷酸合成酶的活性。阿非科林是DNA聚合酶α的抑制剂，但不是胸苷酸合成酶的抑制剂，在加入[5-³H]脱氧尿苷后再添加到细胞中时，会导致该酶随时间依赖性抑制。在加入[5-³H]脱氧尿苷之前，先用羟基脲和阿非科林依次处理细胞，其胸苷酸合成酶的初始活性较高，并随时间降低。这种模式表明胸苷酸合成酶活性与DNA合成有关；然而，其被抑制DNA合成的药物所抑制，可能是由于胸苷核苷酸的积累，而不是由于复制酶复合物中的变构相互作用。