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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Effective intra-S checkpoint responses to UVC in primary human melanocytes and melanoma cell lines.

Authors: Cordeiro-Stone, Marila; McNulty, John J; Sproul, Christopher D; Chastain, Paul D; Gibbs-Flournoy, Eugene; Zhou, Yingchun; Carson, Craig; Rao, Shangbang; Mitchell, David L; Simpson, Dennis A; Thomas, Nancy E; Ibrahim, Joseph G; Kaufmann, William K

Published In Pigment Cell Melanoma Res, (2016 Jan)

Abstract: The objective of this study was to assess potential functional attenuation or inactivation of the intra-S checkpoint during melanoma development. Proliferating cultures of skin melanocytes, fibroblasts, and melanoma cell lines were exposed to increasing fluences of UVC and intra-S checkpoint responses were quantified. Melanocytes displayed stereotypic intra-S checkpoint responses to UVC qualitatively and quantitatively equivalent to those previously demonstrated in skin fibroblasts. In comparison with fibroblasts, primary melanocytes displayed reduced UVC-induced inhibition of DNA strand growth and enhanced degradation of p21Waf1 after UVC, suggestive of enhanced bypass of UVC-induced DNA photoproducts. All nine melanoma cell lines examined, including those with activating mutations in BRAF or NRAS oncogenes, also displayed proficiency in activation of the intra-S checkpoint in response to UVC irradiation. The results indicate that bypass of oncogene-induced senescence during melanoma development was not associated with inactivation of the intra-S checkpoint response to UVC-induced DNA replication stress.

PubMed ID: 26437005 Exiting the NIEHS site

MeSH Terms: Biomarkers/metabolism; Cell Line; Checkpoint Kinase 1; DNA Damage; DNA Repair/radiation effects; DNA Replication/radiation effects; DNA-Directed DNA Polymerase/metabolism; Diploidy; Dose-Response Relationship, Radiation; Fibroblasts/radiation effects; Humans; Melanins/metabolism; Melanocytes/cytology*; Melanocytes/radiation effects*; Melanoma/pathology*; Phosphorylation/radiation effects; Protein Kinases/metabolism; Pyrimidine Dimers/metabolism; S Phase Cell Cycle Checkpoints/radiation effects*; Ultraviolet Rays*

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