TY - JOUR
T1 - The protective role of DOT1L in UV-induced melanomagenesis
AU - Zhu, Bo
AU - Chen, Shuyang
AU - Wang, Hongshen
AU - Yin, Chengqian
AU - Han, Changpeng
AU - Peng, Cong
AU - Liu, Zhaoqian
AU - Wan, Lixin
AU - Zhang, Xiaoyang
AU - Zhang, Jie
AU - Lian, Christine G.
AU - Ma, Peilin
AU - Xu, Zhi Xiang
AU - Prince, Sharon
AU - Wang, Tao
AU - Gao, Xiumei
AU - Shi, Yujiang
AU - Liu, Dali
AU - Liu, Min
AU - Wei, Wenyi
AU - Wei, Zhi
AU - Pan, Jingxuan
AU - Wang, Yongjun
AU - Xuan, Zhenyu
AU - Hess, Jay
AU - Hayward, Nicholas K.
AU - Goding, Colin R.
AU - Chen, Xiang
AU - Zhou, Jun
AU - Cui, Rutao
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The 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.
AB - The 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.
UR - https://www.scopus.com/pages/publications/85041386453
UR - https://www.scopus.com/pages/publications/85041386453#tab=citedBy
U2 - 10.1038/s41467-017-02687-7
DO - 10.1038/s41467-017-02687-7
M3 - Article
C2 - 29343685
AN - SCOPUS:85041386453
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 259
ER -