Abstract
FBH1 is a member of the UvrD family of DNA helicases and plays a crucial role in the response to DNA replication stress. In particular, upon DNA replication stress, FBH1 promotes double-strand breakage and activation of the DNA-PK and ATM signaling cascades in a helicase-dependent manner. In the present manuscript, we show that FBH1 is often deleted or mutated in melanoma cells, which results in their increased survival in response to replicative stress. Accordingly, FBH1 depletion promotes UV-mediated transformation of human melanocytes. Thus, FBH1 inactivation appears to contribute to oncogenic transformation by allowing survival of cells undergoing replicative stress due to external factors such as UV irradiation.
Keywords:
DNA replication stress; F-box protein; FBH1; helicase; melanoma.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Survival / drug effects
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Cell Survival / radiation effects
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Cell Transformation, Neoplastic / radiation effects
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Cells, Cultured
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DNA Breaks, Double-Stranded / drug effects
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DNA Breaks, Double-Stranded / radiation effects
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DNA Helicases / antagonists & inhibitors
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DNA Helicases / genetics
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DNA Helicases / metabolism*
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DNA Replication
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Humans
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Hydroxyurea / pharmacology
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Melanocytes / cytology
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Melanocytes / metabolism*
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Melanoma / metabolism*
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Melanoma / pathology
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Mutation
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RNA Interference
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RNA, Small Interfering / metabolism
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Signal Transduction / drug effects
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Ultraviolet Rays
Substances
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DNA-Binding Proteins
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RNA, Small Interfering
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DNA Helicases
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FBH1 protein, human
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Hydroxyurea