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  • FBH1 protects melanocytes from transformation and is deregulated in melanomas.

FBH1 protects melanocytes from transformation and is deregulated in melanomas.

Cell cycle (Georgetown, Tex.) (2013-03-08)
Yeon-Tae Jeong, Lukas Cermak, Maria V Guijarro, Eva Hernando, Michele Pagano
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.