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氮杂胞苷诱导中国仓鼠卵巢细胞中一个DNA修复基因的重新激活。

Azacytidine-induced reactivation of a DNA repair gene in Chinese hamster ovary cells.

作者信息

Jeggo P A, Holliday R

出版信息

Mol Cell Biol. 1986 Aug;6(8):2944-9. doi: 10.1128/mcb.6.8.2944-2949.1986.

Abstract

Six X-ray-sensitive (xrs) strains of the CHO-K1 cell line were shown to revert at a very high frequency after treatment with 5-azacytidine. This suggested that there was a methylated xrs+ gene in these strains which was structurally intact, but not expressed. The xrs strains did not complement one another, and the locus was autosomally located. In view of the frequency of their isolation and their somewhat different phenotypes, we propose that the xrs strains are mutants derived from an active wild-type gene. However, there is in addition a methylated silent gene present in the genome. Azacytidine treatment reactivated this gene. We present a model for the functional hemizygosity of mammalian cell lines, which is based on the inactivation of genes by de novo hypermethylation. In contrast to results with xrs strains, other repair-defective lines were found not to be reverted by azacytidine.

摘要

CHO-K1细胞系的六个对X射线敏感(xrs)的菌株在用5-氮杂胞苷处理后显示出极高频率的回复突变。这表明在这些菌株中存在一个甲基化的xrs+基因,其结构完整但未表达。xrs菌株之间不能互补,该基因座位于常染色体上。鉴于它们的分离频率和有些不同的表型,我们提出xrs菌株是源自一个活性野生型基因的突变体。然而,基因组中还存在一个甲基化的沉默基因。氮杂胞苷处理使该基因重新激活。我们提出了一个基于基因从头超甲基化导致基因失活的哺乳动物细胞系功能半合子模型。与xrs菌株的结果相反,发现其他修复缺陷型细胞系不会被氮杂胞苷回复突变。

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