The protective role of DOT1L in UV-induced melanomagenesis

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dc.contributor.authorYin, Chengqian
dc.contributor.authorZhang, Jie
dc.contributor.authorWei, Wenyi
dc.contributor.authorWei, Zhi
dc.contributor.authorPan, Jingxuan
dc.contributor.authorWang, Yongjun
dc.contributor.authorXuan, Zhenyu
dc.contributor.authorHess, Jay
dc.contributor.authorHayward, Nicholas K
dc.contributor.authorGoding, Colin R
dc.contributor.authorChen, Xiang
dc.contributor.authorZhou, Jun
dc.contributor.authorCui, Rutao
dc.date.accessioned2021-10-08T07:08:26Z
dc.date.available2021-10-08T07:08:26Z
dc.date.issued2018
dc.description.abstractThe 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.
dc.identifier.apacitationYin, C., Zhang, J., Wei, W., Wei, Z., Pan, J., Wang, Y., ... Cui, R. (2018). The protective role of DOT1L in UV-induced melanomagenesis. <i>Nature Communications</i>, 9(1), 174 - 177. http://hdl.handle.net/11427/34582en_ZA
dc.identifier.chicagocitationYin, Chengqian, Jie Zhang, Wenyi Wei, Zhi Wei, Jingxuan Pan, Yongjun Wang, Zhenyu Xuan, et al "The protective role of DOT1L in UV-induced melanomagenesis." <i>Nature Communications</i> 9, 1. (2018): 174 - 177. http://hdl.handle.net/11427/34582en_ZA
dc.identifier.citationYin, C., Zhang, J., Wei, W., Wei, Z., Pan, J., Wang, Y., Xuan, Z. & Hess, J. et al. 2018. The protective role of DOT1L in UV-induced melanomagenesis. <i>Nature Communications.</i> 9(1):174 - 177. http://hdl.handle.net/11427/34582en_ZA
dc.identifier.issn2041-1723
dc.identifier.ris TY - Journal Article AU - Yin, Chengqian AU - Zhang, Jie 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 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. DA - 2018 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Nature Communications LK - https://open.uct.ac.za PY - 2018 SM - 2041-1723 T1 - The protective role of DOT1L in UV-induced melanomagenesis TI - The protective role of DOT1L in UV-induced melanomagenesis UR - http://hdl.handle.net/11427/34582 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34582
dc.identifier.vancouvercitationYin C, Zhang J, Wei W, Wei Z, Pan J, Wang Y, et al. The protective role of DOT1L in UV-induced melanomagenesis. Nature Communications. 2018;9(1):174 - 177. http://hdl.handle.net/11427/34582.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Human Biology
dc.publisher.facultyFaculty of Health Sciences
dc.sourceNature Communications
dc.source.journalissue1
dc.source.journalvolume9
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1038/s41467-017-02687-7
dc.subject.otherAnimals
dc.subject.otherCarcinogenesis
dc.subject.otherCells, Cultured
dc.subject.otherDNA Repair
dc.subject.otherDNA-Binding Proteins
dc.subject.otherHumans
dc.subject.otherLoss of Function Mutation
dc.subject.otherMelanoma
dc.subject.otherMethyltransferases
dc.subject.otherMice
dc.subject.otherMice, Knockout
dc.subject.otherProto-Oncogene Proteins B-raf
dc.subject.otherUltraviolet Rays
dc.subject.otherDNA-Binding Proteins
dc.subject.otherXPC protein, human
dc.subject.otherDOT1L protein, human
dc.titleThe protective role of DOT1L in UV-induced melanomagenesis
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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