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Differential repair of DNA damage in the human metallothionein gene family.

机译:人类金属硫蛋白基因家族中DNA损伤的差异修复。

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We studied the repair of UV- and aflatoxin B1 (AFB1)-induced damage in the human metallothionein (hMT) gene family. After exposure to either UV or AFB1, DNA damage was initially repaired faster in the DNA fragments containing the transcribed hMT-IA, hMT-IE, and hMT-IIA genes than in the genome overall. By 6 h posttreatment, there was at least twice as much repair in these genes as in the rest of the genome. Repair of UV damage in the hMT-IB gene, which shows cell-type specific expression, and in the hMT-IIB gene, which is a nontranscribed processed pseudogene, was about the same as in the rest of the genome, whereas repair of AFB1-induced damage was deficient in these two genes. Inducing transcription of the three expressed hMT genes with CdCl2 or of only the hMT-IIA gene with dexamethasone increased the initial rate of repair in the induced genes another twofold over the rate observed when they were transcribed at a basal level. The rates of repair in the hMT-IB and hMT-IIB genes were not altered by these inducing treatments. Transcription of the hMT genes was transiently inhibited after UV irradiation. Inducing transcription of the genes did not shorten this UV-induced delay. Thus, the efficiency of repair of damage in a DNA sequence is dependent on the level of transcriptional activity associated with that sequence. However, an increased efficiency in repair of a gene itself is not necessarily coupled to recovery of its transcription after DNA damage.
机译:我们研究了人类金属硫蛋白(hMT)基因家族中UV和黄曲霉毒素B1(AFB1)诱导的损伤的修复。暴露于UV或AFB1后,包含转录的hMT-IA,hMT-IE和hMT-IIA基因的DNA片段中的DNA损伤修复速度要比整个基因组更快。后处理6小时,这些基因的修复至少是基因组其余部分修复的两倍。 hMT-IB基因和非转录的加工假基因hMT-IIB基因中的紫外线损伤修复与基因组其余部分大致相同,而AFB1的修复在这两个基因中引起的损伤是不足的。用CdCl2诱导三个表达的hMT基因转录,或用地塞米松诱导仅hMT-IIA基因转录,诱导的基因修复的初始修复率比它们在基础水平转录时的修复率高出两倍。这些诱导治疗未改变hMT-IB和hMT-IIB基因的修复率。在紫外线照射后,hMT基因的转录被暂时抑制。诱导基因转录并没有缩短紫外线诱导的延迟。因此,修复DNA序列中的损伤的效率取决于与该序列相关的转录活性的水平。但是,基因本身修复效率的提高不一定与DNA损伤后其转录的恢复有关。

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