The protective role of DOT1L in UV-induced melanomagenesis

Bo Zhu; Shuyang Chen; Hongshen Wang; Chengqian Yin; Changpeng Han; Cong Peng; Zhaoqian Liu; Lixin Wan; Xiaoyang Zhang; Jie Zhang; Christine G. Lian; Peilin Ma; Zhi Xiang Xu; Sharon Prince; Tao Wang; Xiumei Gao; Yujiang Shi; Dali Liu; Min Liu; Wenyi Wei; Zhi Wei; Jingxuan Pan; Yongjun Wang; Zhenyu Xuan; Jay Hess; Nicholas K. Hayward; Colin R. Goding; Xiang Chen; Jun Zhou; Rutao Cui

doi:10.1038/s41467-017-02687-7

The protective role of DOT1L in UV-induced melanomagenesis

Bo Zhu, Shuyang Chen, Hongshen Wang, Chengqian Yin, Changpeng Han, Cong Peng, Zhaoqian Liu, Lixin Wan, Xiaoyang Zhang, Jie Zhang, Christine G. Lian, Peilin Ma, Zhi Xiang Xu, Sharon Prince, Tao Wang, Xiumei Gao, Yujiang Shi, Dali Liu, Min Liu, Wenyi WeiZhi Wei, Jingxuan Pan, Yongjun Wang, Zhenyu Xuan, Jay Hess, Nicholas K. Hayward, Colin R. Goding, Xiang Chen, Jun Zhou, Rutao Cui

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

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.

Original language	English (US)
Article number	259
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02687-7
State	Published - Dec 1 2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-017-02687-7

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@article{57599ea0a3af4ad599961c5a07eee222,

title = "The protective role of DOT1L in UV-induced melanomagenesis",

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.",

author = "Bo Zhu and Shuyang Chen and Hongshen Wang and Chengqian Yin and Changpeng Han and Cong Peng and Zhaoqian Liu and Lixin Wan and Xiaoyang Zhang and Jie Zhang and Lian, {Christine G.} and Peilin Ma and Xu, {Zhi Xiang} and Sharon Prince and Tao Wang and Xiumei Gao and Yujiang Shi and Dali Liu and Min Liu and Wenyi Wei and Zhi Wei and Jingxuan Pan and Yongjun Wang and Zhenyu Xuan and Jay Hess and Hayward, {Nicholas K.} and Goding, {Colin R.} and Xiang Chen and Jun Zhou and Rutao Cui",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-017-02687-7",

language = "English (US)",

volume = "9",

journal = "Nature communications",

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Zhu, B, Chen, S, Wang, H, Yin, C, Han, C, Peng, C, Liu, Z, Wan, L, Zhang, X, Zhang, J, Lian, CG, Ma, P, Xu, ZX, Prince, S, Wang, T, Gao, X, Shi, Y, Liu, D, Liu, M, Wei, W, Wei, Z, Pan, J, Wang, Y, Xuan, Z, Hess, J, Hayward, NK, Goding, CR, Chen, X, Zhou, J & Cui, R 2018, 'The protective role of DOT1L in UV-induced melanomagenesis', Nature communications, vol. 9, no. 1, 259. https://doi.org/10.1038/s41467-017-02687-7

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

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.

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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 -

The protective role of DOT1L in UV-induced melanomagenesis

Abstract

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