A CRISPR-Cas9 knock-out screening identified additional candidate genes whose ablation conferred resistance to BRAF inhibitor in melanoma cell line, including neurofibromin 2 (NF2), Cullin 3 E3 ligase (CUL3), and members of the STAGA histone acetyltransferase complex (TADA1 and TADA2B). Here, CUL3 is linked to melanoma.