Antifolate-induced misincorporation of deoxyuridine monophosphate into DNA by cells from patients with the fragile X syndrome.
Antifolate-induced misincorporation of deoxyuridine monophosphate into DNA by cells from patients with the fragile X syndrome.
复制标题
抗叶酸剂诱导脆性 X 综合征患者细胞将脱氧尿苷单磷酸错误掺入 DNA。
DOI：
10.1002/ajmg.1320210410
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Erbe,RW
中科院分区：
文献类型：
--
作者：
Wang,JC;Beardsley,GP;Erbe,RW
Xq27 上的脆弱位点在导致细胞内胸苷三磷酸浓度降低的条件下在体外表达，这种条件也被证明会促进脱氧尿苷单磷酸 (dUMP) 取代胸苷错误掺入 DNA。我们测试了 dUMP 的全细胞错误掺入增加作为脆性 X 异常表达的可能分子机制。脱氧尿苷三磷酸酶和尿嘧啶-DNA-糖基化酶（这两种通常阻止 dUMP 在 DNA 中积累的酶）在脆性 X 综合征细胞中都不存在缺陷。在正常和脆性 X 综合征淋巴母细胞中，dUMP 的错误掺入水平相对较低。尽管这些结果提供了强有力的证据，反对脆性 X 综合征细胞中 dUMP 普遍错误掺入，但在这些含有二倍体染色体补体的整个细胞的研究中，可能无法检测到 Xq27 处存在的实质性差异。
The fragile site at Xq27 is expressed in vitro under conditions that lead to decreased intracellular thymidine triphosphate concentration, a condition which has also been shown to promote the misincorporation into DNA of deoxyuridine monophosphate (dUMP) in place of thymidine. We tested for increased whole‐cell misincorporation of dUMP as a possible molecular mechanism for the expression of the fragile X abnormality. Neither deoxyuridine triphosphatase nor uracil‐DNA‐glycosylase, the two enzymes that normally prevent the accumulation of dUMP in DNA, was deficient in fragile X syndrome cells. Misincorporation of dUMP occurred in comparably low levels in both normal and fragile X syndrome lymphoblasts. Although these results provide strong evidence against generalized misincorporation of dUMP in fragile X syndrome cells, a substantial real difference present at Xq27 might not be detected in these studies of whole cells containing the diploid chromosome complement.