The protective role of DOT1L in UV-induced melanomagenesis
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 gen...
| Huvudupphovsmän: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Materialtyp: | Journal article |
| Språk: | English |
| Publicerad: |
Springer Nature
2018
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| _version_ | 1826307135969951744 |
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| author | Zhu, B Chen, S Wang, H Yin, C Han, C Peng, C Liu, Z Wan, L Zhang, X Zhang, J Lian, C Ma, P Xu, Z 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, N Goding, C Chen, X Zhou, J Cui, R |
| author_facet | Zhu, B Chen, S Wang, H Yin, C Han, C Peng, C Liu, Z Wan, L Zhang, X Zhang, J Lian, C Ma, P Xu, Z 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, N Goding, C Chen, X Zhou, J Cui, R |
| author_sort | Zhu, B |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:58:24Z |
| format | Journal article |
| id | oxford-uuid:feeb4081-a35d-4096-a89e-d9a6e90fcca2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:58:24Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:feeb4081-a35d-4096-a89e-d9a6e90fcca22022-03-27T13:40:31ZThe protective role of DOT1L in UV-induced melanomagenesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:feeb4081-a35d-4096-a89e-d9a6e90fcca2EnglishSymplectic Elements at OxfordSpringer Nature2018Zhu, BChen, SWang, HYin, CHan, CPeng, CLiu, ZWan, LZhang, XZhang, JLian, CMa, PXu, ZPrince, SWang, TGao, XShi, YLiu, DLiu, MWei, WWei, ZPan, JWang, YXuan, ZHess, JHayward, NGoding, CChen, XZhou, JCui, RThe 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. |
| spellingShingle | Zhu, B Chen, S Wang, H Yin, C Han, C Peng, C Liu, Z Wan, L Zhang, X Zhang, J Lian, C Ma, P Xu, Z 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, N Goding, C Chen, X Zhou, J Cui, R The protective role of DOT1L in UV-induced melanomagenesis |
| title | The protective role of DOT1L in UV-induced melanomagenesis |
| title_full | The protective role of DOT1L in UV-induced melanomagenesis |
| title_fullStr | The protective role of DOT1L in UV-induced melanomagenesis |
| title_full_unstemmed | The protective role of DOT1L in UV-induced melanomagenesis |
| title_short | The protective role of DOT1L in UV-induced melanomagenesis |
| title_sort | protective role of dot1l in uv induced melanomagenesis |
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