DDB1 is essential for genomic stability in developing epidermis.
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.
Cang
Yong
Y
Howard Hughes Medical Institute and Departments of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Zhang
Jianxuan
J
Nicholas
Sally A
SA
Kim
Arianna L
AL
Zhou
Pengbo
P
Goff
Stephen P
SP
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism*; D017353:Gene Deletion; D042822:Genomic Instability; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C490415:Ddb1 protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D016159:Tumor Suppressor Protein p53