Zhu, BoChen, ShuyangWang, HongshenYin, ChengqianHan, ChangpengPeng, CongLiu, ZhaoqianWan, LixinZhang, XiaoyangZhang, JieLian, ChristineMa, PeilinXu, Zhi-xiangPrince, SharonWang, TaoGao, XiumeiShi, YujiangLiu, DaliLiu, MinWei, WenyiWei, ZhiPan, JingxuanWang, YongjunXuan, ZhenyuHess, JayHayward, Nicholas K.Goding, Colin R.Chen, XiangZhou, JunCui, Rutao2018-02-262018Zhu, B., S. Chen, H. Wang, C. Yin, C. Han, C. Peng, Z. Liu, et al. 2018. “The protective role of DOT1L in UV-induced melanomagenesis.” Nature Communications 9 (1): 259. doi:10.1038/s41467-017-02687-7. http://dx.doi.org/10.1038/s41467-017-02687-7.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868836The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis.en-USJournal Article2018-02-2610.1038/s41467-017-02687-7