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在小鼠皮肤中发现了 DNA 修复基因 Ercc1 的一种新转录本。

A novel transcript for DNA repair gene Ercc1 in mouse skin.

机构信息

Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Western General Hospital, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.

出版信息

Transgenic Res. 2011 Feb;20(1):109-22. doi: 10.1007/s11248-010-9396-3. Epub 2010 Apr 21.

Abstract

The nucleotide excision repair pathway deals with UV-induced DNA damage. The tissue that receives by far the greatest exposure to UV is the skin and we have investigated the possibility that expression of the nucleotide excision repair gene, Ercc1, may display different properties in the skin to deal with a more demanding role in that tissue. ERCC1, in a complex with XPF, is the structure--specific endonuclease responsible for incising 5' to the UV-induced lesion. We identified a novel Ercc1 mRNA in mouse skin that originates from an alternative upstream promoter. Levels of this skin-specific transcript were low in embryonic skin and increased rapidly after birth, but there was no induction by UV, either in adult skin, or in a cultured keratinocyte model. Levels of the skin-specific Ercc1 transcript were higher in albino than pigmented mouse strains, but there was no difference in ERCC1 protein levels and the expression of the skin-specific transcript was found to be determined by the Ercc1 gene sequence rather than by coat pigmentation. Using an Ercc1 transgene the promoter for the skin-specific transcript was mapped to a region around 400 bp upstream of the normal promoter, where a transposable element with known promoter activity was found in albino but not in pigmented strains.

摘要

核苷酸切除修复途径处理紫外线诱导的 DNA 损伤。迄今为止,皮肤受到的紫外线照射最多,我们研究了核苷酸切除修复基因 Ercc1 的表达是否可能在皮肤中表现出不同的特性,以应对该组织中更具挑战性的角色。ERCC1 与 XPF 形成复合物,是负责在 UV 诱导损伤的 5'端切割的结构特异性内切酶。我们在小鼠皮肤中鉴定出一种新的 Ercc1 mRNA,它来源于一个替代的上游启动子。这种皮肤特异性转录本在胚胎皮肤中的水平较低,出生后迅速增加,但在成年皮肤或培养的角质形成细胞模型中,无论是紫外线诱导还是紫外线诱导,都没有诱导作用。白化鼠比色素沉着鼠的皮肤特异性 Ercc1 转录本水平更高,但 ERCC1 蛋白水平没有差异,皮肤特异性转录本的表达是由 Ercc1 基因序列决定的,而不是由毛色决定的。使用 Ercc1 转基因,皮肤特异性转录本的启动子被定位到正常启动子上游约 400 bp 的区域,在白化鼠中发现了一个具有已知启动子活性的可移动元件,但在色素沉着鼠中没有发现。

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