title: Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity.
abstract: The oncogenic BRAF(V600E) mutation is common in melanomas as well as moles. The roles that this mutation plays in the early events in the development of melanoma are poorly understood. This study demonstrates that expression of BRAF(V600E) is not only clastogenic, but synergizes for clastogenesis caused by exposure to ultraviolet radiation in the 300 to 320 nM (UVB) range. Expression of BRAF(V600E) was associated with induction of Chk1 pS280 and a reduction in chromatin remodeling factors BRG1 and BAF180. These alterations in the Chk1 signaling pathway and SWI/SNF chromatin remodeling pathway may contribute to the clastogenesis and UVB sensitivity. These results emphasize the importance of preventing sunburns in children with developing moles.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dennis@email.unc.edu.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dennis@email.unc.edu.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Simpson
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. nlemoine@live.unc.edu.
authors.forename: Nathalay
authors.initials: N
authors.lastname: Lemonie
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dscardamone@gmail.com.
authors.forename: David S
authors.initials: DS
authors.lastname: Morgan
authors.affiliation: Department of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, WA 99210, USA. shobhan.gaddameedhi@wsu.edu.
authors.forename: Shobhan
authors.initials: S
authors.lastname: Gaddameedhi
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. wkarlk@med.unc.edu.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. wkarlk@med.unc.edu.|Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. wkarlk@med.unc.edu.
authors.forename: William K
authors.initials: WK
authors.lastname: Kaufmann
keywords: BRAF(V600E); UVB; melanocytes; melanoma