The Protective Role of Dot1L in UV-Induced Melanomagenesis

dc.contributor.ORCID0000-0001-9344-8493 (Xuan, Z)en_US
dc.contributor.authorZhu, Boen_US
dc.contributor.authorChen, Shuyangen_US
dc.contributor.authorWang, Hongshenen_US
dc.contributor.authorYin, Chengqianen_US
dc.contributor.authorHan, Changpengen_US
dc.contributor.authorPeng, Congen_US
dc.contributor.authorLiu, Zhaoqianen_US
dc.contributor.authorWan, Lixinen_US
dc.contributor.authorZhang, Xiaoyangen_US
dc.contributor.authorZhang, Jieen_US
dc.contributor.authorLian, Christine G.en_US
dc.contributor.authorMa, Peilinen_US
dc.contributor.authorXu, Zhi-xiangen_US
dc.contributor.authorPrince, Sharonen_US
dc.contributor.authorWang, Taoen_US
dc.contributor.authorGao, Xiumeien_US
dc.contributor.authorShi, Yujiangen_US
dc.contributor.authorLiu, Dalien_US
dc.contributor.authorLiu, Minen_US
dc.contributor.authorWei, Wenyien_US
dc.contributor.authorWei, Zhien_US
dc.contributor.authorPan, Jingxuanen_US
dc.contributor.authorWang, Yongjunen_US
dc.contributor.authorXuan, Zhenyuen_US
dc.contributor.authorHess, Jayen_US
dc.contributor.authorHayward, Nicholas K.en_US
dc.contributor.authorGoding, Colin R.en_US
dc.contributor.authorChen, Xiangen_US
dc.contributor.authorZhou, Junen_US
dc.contributor.authorCui, Rutaoen_US
dc.contributor.utdAuthorXuan, Zhenyuen_US
dc.date.accessioned2018-11-05T21:07:17Z
dc.date.available2018-11-05T21:07:17Z
dc.date.created2018-01-17en_US
dc.date.issued2018-11-05
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.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorship"This work was supported by the National Key R&D Program of China (2017YFA0503502) and the National Natural Science Foundation of China (31730050). This work was also supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research Program under Award No. W81XWH-15-1-0109; Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China (Grant No.81428025 for R.C.); Major Projects of international Cooperation and Exchanges from National Natural Science Foundation of China (81620108024), and National Natural Science Foundation of China (81572679, 81630106); Innovative Research Team in University of Ministry of Education of China (IRT1270); Microarray was performed by the Boston University Microarray Sequencing Resource (CTSA grant UL1-TR001430).en_US
dc.identifier.bibliographicCitationZhu, Bo, Shuyang Chen, Hongshen Wang, Chengqian Yin, et al. 2018. "The protective role of DOT1L in UV-induced melanomagenesis." Nature Communications 9, doi:10.1038/s41467-017-02687-7en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6282
dc.identifier.volume9en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urihttp://dx.doi.org/10.1038/s41467-017-02687-7
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2018 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNature Communications
dc.subjectLeukemiaen_US
dc.subjecthistone H3 trimethyl Lys4en_US
dc.subjectMethylationen_US
dc.subjectMelanomaen_US
dc.subjectTransgenic miceen_US
dc.subjectDNA damageen_US
dc.subjectChromatinen_US
dc.subjectMutationen_US
dc.subjectDOT1L proteinen_US
dc.titleThe Protective Role of Dot1L in UV-Induced Melanomagenesisen_US
dc.type.genrearticleen_US

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