title: Thymidine dinucleotide mimics the effect of solar simulated irradiation on p53 and p53-regulated proteins.
abstract: The tumor suppressor protein p53 participates in DNA repair and cell cycle regulation in response to injuries like ultraviolet (UV) irradiation. We have previously reported that the thymidine dinucleotide (pTpT), a common target for DNA photoproduct formation by UV light, mimics many effects of UV irradiation in cultured skin-derived cells, at least in part through the activation of p53. In this report we compare the effects of solar-simulated irradiation and pTpT on p53 and p53-regulated proteins involved in cellular growth arrest and DNA repair in cultured human dermal fibroblasts. We find that, like UV irradiation, pTpT increases the levels of p53, p21, and proliferating-cell nuclear antigen. The magnitude and time course of the inductions are UV dose dependent and consistent with known regulatory interactions among these nuclear proteins. These data confirm and expand previous studies of UV effects on nuclear proteins involved in cell cycle regulation and DNA repair. Our observations suggest that such protective effects can also be induced by pTpT in the absence of initial DNA damage, rendering cells more capable of responding to subsequent DNA damage.
authors.affiliation: Department of Dermatology, Boston University School of Medicine, Massachusetts 02118, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Goukassian
authors.forename: M S
authors.initials: MS
authors.lastname: Eller
authors.forename: M
authors.initials: M
authors.lastname: Yaar
authors.forename: B A
authors.initials: BA
authors.lastname: Gilchrest
mesh_terms: D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004260:DNA Repair; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D015226:Dinucleoside Phosphates; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C017758:thymidylyl-(3'-5')-thymidine