title: FBH1 protects melanocytes from transformation and is deregulated in melanomas.
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.
authors: Department of Pathology, NYU Cancer Institute, New York University School of Medicine, New York, NY, USA.
authors: Yeon-Tae
authors: YT
authors: Jeong
authors: Lukas
authors: L
authors: Cermak
authors: Maria V
authors: MV
authors: Guijarro
authors: Eva
authors: E
authors: Hernando
authors: Michele
authors: M
authors: Pagano
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D004265:DNA Helicases; C464443:FBH1 protein, human; D006918:Hydroxyurea
keywords: DNA replication stress; F-box protein; FBH1; helicase; melanoma