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PMID: 9356500 Published · ppublish English Journal Article

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 23 ·1997-11-11 ·Pages 12627-32

Eller MS, Maeda T, Magnoni C, Atwal D, Gilchrest BA

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.

MeSH Terms
Cells, Cultured DNA Damage/radiation effects DNA Repair/drug effects Humans Infant, Newborn Keratinocytes/pathology,physiology Oligonucleotides/pharmacology Skin Physiological Phenomena Thymidine/pharmacology Tumor Suppressor Protein p53/physiology Ultraviolet Rays
Chemicals
Oligonucleotides Tumor Suppressor Protein p53 Thymidine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Eller M S
Boston University Medical School, Department of Dermatology, Boston, MA 02118-2394, USA.
Maeda T
Magnoni C
Atwal D
Gilchrest B A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.23.12627
Published
1997-11-11
Pages
12627-32
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC25061
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.23.12627 PMC Full Text View journal details
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