GammaH2AX, an accurate marker that analyzes UV genotoxic effects on human keratinocytes and on human skin

The phosphorylated form of histone H2AX, gammaH2AX, is a component of the DNA repair system. Most studies have focused on the role of gammaH2AX during cell transformation and human cancer, but little is known about its role in keratinocytes and the skin during UV irradiation. We analyzed the respons...

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Veröffentlicht in:Photochemistry and photobiology 2010-07, Vol.86 (4), p.933-941
Hauptverfasser: Barnes, Laurent, Dumas, Marc, Juan, Mylène, Noblesse, Emmanuelle, Tesniere, Anne, Schnebert, Sylvianne, Guillot, Bernard, Molès, Jean-Pierre
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container_end_page 941
container_issue 4
container_start_page 933
container_title Photochemistry and photobiology
container_volume 86
creator Barnes, Laurent
Dumas, Marc
Juan, Mylène
Noblesse, Emmanuelle
Tesniere, Anne
Schnebert, Sylvianne
Guillot, Bernard
Molès, Jean-Pierre
description The phosphorylated form of histone H2AX, gammaH2AX, is a component of the DNA repair system. Most studies have focused on the role of gammaH2AX during cell transformation and human cancer, but little is known about its role in keratinocytes and the skin during UV irradiation. We analyzed the response to UV irradiation focusing on the phosphorylation of histone H2AX both in vitro, in keratinocyte cultures and in artificial epidermis, and then in vivo, in human skin. Acute UVB irradiation of human keratinocytes increased the phosphorylation of H2AX in a dose-dependent manner; two types of gammaH2AX response were observed either in vitro or in vivo. After a low nonapoptotic UVB irradiation, cells contained phosphorylated H2AX and arrested their cell cycle to repair the DNA damages. For a stronger and proapoptotic UVB irradiation, keratinocytes dramatically increased the phosphorylation of H2AX and committed apoptosis. Our results indicate that gammaH2AX constitutes a highly sensitive marker relevant for studying subapoptotic doses as well as proapoptotic doses of UVB in human skin.
doi_str_mv 10.1111/j.1751-1097.2010.00744.x
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Apoptosis - radiation effects
Biomarkers - analysis
Biomarkers - metabolism
Cells, Cultured
DNA - genetics
DNA - radiation effects
DNA Damage
DNA Repair
Dose-Response Relationship, Radiation
Histones - analysis
Histones - genetics
Histones - metabolism
Humans
Keratinocytes - metabolism
Keratinocytes - radiation effects
Phosphorylation
Skin - metabolism
Skin - radiation effects
Ultraviolet Rays
title GammaH2AX, an accurate marker that analyzes UV genotoxic effects on human keratinocytes and on human skin
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