DDB1 is essential for genomic stability in developing epidermis
DDB1 is essential for genomic stability in developing epidermis
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DOI：
10.1073/pnas.0611311104
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发表时间：
2007-02-20
影响因子：
11.1
通讯作者：
Goff, Stephen P.
中科院分区：
文献类型：
--
作者：
Cang, Yong;Zhang, Jianxuan;Goff, Stephen P.
哺乳动物的表皮是通过表皮前体细胞的增殖和分化来维持的，这是一种刻板的发育程序。在这里，我们报道了紫外线损伤的小鼠表皮中DNA结合蛋白1[DDB1]的组织特异性缺失导致c-jun和p21Cip1的显著积累，细胞周期停滞在G(2)/M，增殖细胞选择性地凋亡，结果是几乎完全丧失了表皮和毛囊。P53肿瘤抑制基因的缺失部分挽救了上皮祖细胞的死亡，并允许非整倍体细胞在表皮中积累。我们的结果表明，DDB1通过控制细胞周期调节水平，从而维持基因组的稳定，在发育过程中发挥着重要作用。
The mammalian epidermis is maintained by proliferation and differentiation of epidermal progenitor cells in a stereotyped developmental program. Here we report that tissue-specific deletion of the UV-damaged DNA-binding protein 1 [DDB1) in mouse epidermis led to dramatic accumulation of c-Jun and p21Cip1, arrest of cell cycle at G(2)/M, selective apoptosis of proliferating cells, and as a result, a nearly complete loss of the epidermis and hair follicles. Deletion of the p53 tumor suppressor gene partially rescued the epithelial progenitor cells from death and allowed for the accumulation of aneuploid cells in the epidermis. Our results suggest that DDB1 plays an important role in development by controlling levels of cell cycle regulators and thereby maintaining genomic stability.