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The protective role of DOT1L in UV-induced melanomagenesis

Author

Listed:
  • Bo Zhu

    (Boston University School of Medicine
    Shandong Normal University)

  • Shuyang Chen

    (Boston University School of Medicine
    Central South University)

  • Hongshen Wang

    (Boston University School of Medicine
    Shanghai University of Traditional Chinese Medicine)

  • Chengqian Yin

    (Boston University School of Medicine
    Jiangsu University)

  • Changpeng Han

    (Boston University School of Medicine
    Shanghai University of Traditional Chinese Medicine)

  • Cong Peng

    (Central South University)

  • Zhaoqian Liu

    (Central South University)

  • Lixin Wan

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Xiaoyang Zhang

    (Dana-Farber Cancer Institute)

  • Jie Zhang

    (New Jersey Institute of Technology)

  • Christine G. Lian

    (Harvard Medical School)

  • Peilin Ma

    (Indiana University School of Medicine)

  • Zhi-xiang Xu

    (University of Alabama at Birmingham School of Medicine)

  • Sharon Prince

    (University of Cape Town)

  • Tao Wang

    (Tianjin University of Traditional Chinese Medicine)

  • Xiumei Gao

    (Tianjin University of Traditional Chinese Medicine)

  • Yujiang Shi

    (Harvard Medical School)

  • Dali Liu

    (Loyola University Chicago)

  • Min Liu

    (Shandong Normal University)

  • Wenyi Wei

    (Harvard Medical School)

  • Zhi Wei

    (New Jersey Institute of Technology)

  • Jingxuan Pan

    (Jinan University)

  • Yongjun Wang

    (Shanghai University of Traditional Chinese Medicine)

  • Zhenyu Xuan

    (University of Texas at Dallas)

  • Jay Hess

    (Indiana University School of Medicine)

  • Nicholas K. Hayward

    (QIMR Berghofer Medical Research Institute)

  • Colin R. Goding

    (University of Oxford)

  • Xiang Chen

    (Central South University)

  • Jun Zhou

    (Shandong Normal University)

  • Rutao Cui

    (Boston University School of Medicine)

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.

Suggested Citation

  • 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, 2018. "The protective role of DOT1L in UV-induced melanomagenesis," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02687-7
    DOI: 10.1038/s41467-017-02687-7
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    Cited by:

    1. Cang Li & Zhengyu Wang & Licheng Yao & Xingyu Lin & Yongping Jian & Yujia Li & Jie Zhang & Jingwei Shao & Phuc D. Tran & James R. Hagman & Meng Cao & Yusheng Cong & Hong-yu Li & Colin R. Goding & Zhi-, 2024. "Mi-2β promotes immune evasion in melanoma by activating EZH2 methylation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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