Enhancement of DNA repair in human skin cells by thymidine dinucleotides: Evidence for a p53-mediated mammalian SOS response

被引:171
作者
Eller, MS [1 ]
Maeda, T [1 ]
Magnoni, C [1 ]
Atwal, D [1 ]
Gilchrest, BA [1 ]
机构
[1] BOSTON UNIV, SCH MED, DEPT DERMATOL, BOSTON, MA 02118 USA
关键词
D O I
10.1073/pnas.94.23.12627
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Thymidine dinucleotide (pTpT) stimulates melanogenesis in mammalian pigment cells and intact skin, mimicking the effects of UV irradiation and UV-mimetic DNA damage. Here it is shown that, in addition to tanning, pTpT induces a second photoprotective response, enhanced repair of UV-induced DNA damage. This enhanced repair results in a 2-fold increase in expression of a UV-damaged chloramphenicol acetyltransferase expression vector transfected into pTpT-treated skin fibroblasts and keratinocytes, compared with diluent-treated cells, Direct measurement of thymine dimers and (6-4) photoproducts by immunoassay demonstrates faster repair of both of these UV-induced photoproducts in pTpT-treated fibroblasts. This enhanced repair capacity also improves cell survival and colony-forming ability after irradiation. These effects of pTpT are accomplished, at least in part, by the up-regulation of a set of genes involved in DNA repair (ERCC3 and GADD45) and cell cycle inhibition (SDII). At least two of these genes (GADD45 and SDII) are known to be transcriptionally regulated by the p53 tumor suppressor protein, Here we show that pTpT activates p53, leading to nuclear accumulation of this protein, and also increases the specific binding of this transcription factor to its DNA consensus sequence.
引用
收藏
页码:12627 / 12632
页数:6
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