| First Author | Stout GJ | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 52 | Pages | 18980-5 |
| PubMed ID | 16365302 | Mgi Jnum | J:104713 |
| Mgi Id | MGI:3612663 | Doi | 10.1073/pnas.0505505102 |
| Citation | Stout GJ, et al. (2005) Epidermal transit of replication-arrested, undifferentiated keratinocytes in UV-exposed XPC mice: an alternative to in situ apoptosis. Proc Natl Acad Sci U S A 102(52):18980-5 |
| abstractText | The interplay among nucleotide excision repair, cell-cycle regulation, and apoptosis in the UV-exposed epidermis is extremely important to avoid mutations and malignant transformation. In Xpc(-/-) mice deficient in global genome nucleotide excision repair (GGR), a cell-cycle arrest of epidermal cells in late S-phase [with near-double normal diploid (4N) DNA content] was observed 48-72 h after UV exposure. This arrest resolved without apoptosis (96-168 h). We surmised that these arrested keratinocytes with persistent DNA damage were removed by epidermal turnover. In vivo BrdUrd pulse-chase labeling (>17 h after UV exposure) showed that DNA replication after UV exposure was resumed in Xpc(-/-) mice, but it did not reveal any evidence of retained BrdUrd-labeled S-phase cells in the basal layer of the epidermis at 72 h. Interestingly, by this time a maximum number of cytokeratin 10-negative and cytokeratin 5-positive cells had appeared in the suprabasal epidermal cell layers of UV-exposed Xpc(-/-) mice. Accumulation of these 'basal cell'-like keratinocytes in the suprabasal layers was clearly aberrant and was not observed in WT and heterozygous mice. Flow cytometric analyses of single-cell suspensions from UV-exposed Xpc(-/-) epidermis further showed that the 'near-4N' arrested cells retained cytokeratin 5 and lacked cytokeratin 10. Hence, we conclude that the arrested near-4N cells became detached from the basal layer without entering a proper differentiation program and were indeed subsequently lost through the epidermal turnover. This expulsion apparently constitutes an alternative route, different from in situ apoptosis, to eliminate DNA-damaged arrested cells from the epidermis. |
