The protective role of DOT1L in UV-induced melanomagenesis
Document Type
Article
Publication Date
12-1-2018
Abstract
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.
Identifier
85041386453 (Scopus)
Publication Title
Nature Communications
External Full Text Location
https://doi.org/10.1038/s41467-017-02687-7
e-ISSN
20411723
PubMed ID
29343685
Issue
1
Volume
9
Grant
81428025
Fund Ref
National Cancer Institute
Recommended Citation
Zhu, Bo; Chen, Shuyang; Wang, Hongshen; Yin, Chengqian; Han, Changpeng; Peng, Cong; Liu, Zhaoqian; Wan, Lixin; Zhang, Xiaoyang; Zhang, Jie; Lian, Christine G.; Ma, Peilin; Xu, Zhi Xiang; Prince, Sharon; Wang, Tao; Gao, Xiumei; Shi, Yujiang; and Liu, Dali, "The protective role of DOT1L in UV-induced melanomagenesis" (2018). Faculty Publications. 8238.
https://digitalcommons.njit.edu/fac_pubs/8238
