Okumoto D S, Bohr V A
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892.
Nucleic Acids Res. 1987 Dec 10;15(23):10021-30. doi: 10.1093/nar/15.23.10021.
We have studied DNA repair in the Chinese Hamster Ovary (CHO) metallothionein (MT) gene after UV-light induced damage. The repair was examined comparatively with or without transcriptional activation of the gene by incubation in the presence of the heavy metal ZnCl2. Whereas the repair efficiency was very low in the uninduced state, it increased significantly after induction of the gene. The presence of ZnCl2 did not appear to change other repair parameters in the cells. The overall genome DNA repair efficiency after UV irradiation was similar whether or not the gene was induced and the preferential DNA repair pattern in the essential dihydrofolate reductase (DHFR) gene which we have previously described was unaffected by the presence of ZnCl2. Based upon repair analysis in two different restriction fragments containing the MT I gene, we conclude that the region of efficient repair after induction is considerably larger than the 1 kb size of the gene. The results suggest that the accessibility of a genomic region to DNA repair enzymes may be regulated by the local chromatin structure in a dynamic manner.
我们研究了紫外线诱导损伤后中国仓鼠卵巢(CHO)金属硫蛋白(MT)基因的DNA修复情况。通过在重金属ZnCl₂存在下孵育,比较了该基因转录激活或未激活时的修复情况。在未诱导状态下,修复效率非常低,但基因诱导后显著提高。ZnCl₂的存在似乎并未改变细胞中的其他修复参数。无论该基因是否被诱导,紫外线照射后整个基因组DNA的修复效率相似,并且我们之前描述的必需二氢叶酸还原酶(DHFR)基因中的优先DNA修复模式不受ZnCl₂存在的影响。基于对包含MT I基因的两个不同限制片段的修复分析,我们得出结论,诱导后有效修复的区域比该基因1 kb的大小要大得多。结果表明,基因组区域对DNA修复酶的可及性可能受到局部染色质结构的动态调节。