title: Impaired light detection of the circadian clock in a zebrafish melanoma model.
abstract: The circadian clock controls the timing of the cell cycle in healthy tissues and clock disruption is known to increase tumourigenesis. Melanoma is one of the most rapidly increasing forms of cancer and the precise molecular circadian changes that occur in a melanoma tumor are unknown. Using a melanoma zebrafish model, we have explored the molecular changes that occur to the circadian clock within tumors. We have found disruptions in melanoma clock gene expression due to a major impairment to the light input pathway, with a parallel loss of light-dependent activation of DNA repair genes. Furthermore, the timing of mitosis in tumors is perturbed, as well as the regulation of certain key cell cycle regulators, such that cells divide arhythmically. The inability to co-ordinate DNA damage repair and cell division is likely to promote further tumourigenesis and accelerate melanoma development.
authors.affiliation: a Center for Cell and Molecular Dynamics; Department of Cell and Development Biology ; University College London ; London , UK.
authors.forename: Noémie
authors.initials: N
authors.lastname: Hamilton
authors.forename: Natalia
authors.initials: N
authors.lastname: Diaz-de-Cerio
authors.forename: David
authors.initials: D
authors.lastname: Whitmore
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D008027:Light; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051739:Microphthalmia-Associated Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D056931:Cryptochromes; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D051739:Microphthalmia-Associated Transcription Factor; D056950:Period Circadian Proteins; D029961:Zebrafish Proteins; C541354:clocka protein, zebrafish; C466244:cry1a protein, zebrafish; C497237:mitfa protein, zebrafish; C539026:per1a protein, zebrafish; C498846:per2 protein, zebrafish
keywords: cancer; cell cycle; circadian clock; light input; melanoma; zebrafish
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