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

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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Maeda, T. Eller, M. S. Magnoni, C. Gilchrest, B. A. Atwal, D.
Description	Author Affiliation: Eller MS ( Boston University Medical School, Department of Dermatology, Boston, MA 02118-2394, USA.);
Abstract	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 (SDI1). At least two of these genes (GADD45 and SDI1) 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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Repair Drug Effects Thymidine Pharmacology Tumor Suppressor Protein P53 Physiology Cells, Cultured DNA Damage Radiation Effects Infant, Newborn Keratinocytes Pathology Oligonucleotides Skin Physiological Phenomena Ultraviolet Rays Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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