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 journalArticle

11 Citations (Scopus)

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 languageEnglish (US)
Article number259
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Ultraviolet radiation
ultraviolet radiation
Radiation
DNA Damage
Melanoma
deoxyribonucleic acid
Methyltransferases
mutations
damage
DNA Repair
DNA
Repair
enzyme activity
Mutation
methylation
Methylation
leukemias
lysine
nucleotides
Enzyme activity

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Zhu, B., Chen, S., Wang, H., Yin, C., Han, C., Peng, C., ... Cui, R. (2018). The protective role of DOT1L in UV-induced melanomagenesis. Nature Communications, 9(1), [259]. https://doi.org/10.1038/s41467-017-02687-7

The protective role of DOT1L in UV-induced melanomagenesis. / Zhu, Bo; Chen, Shuyang; Wang, Hongshen; Yin, Chengqian; Han, Changpeng; Peng, Cong; Liu, Zhaoqian; Wan, Lixin; Zhang, Xiaoyang; Zhang, Jie; Lian, Christine G.; Ma, Peilin; Xu, Zhi Xiang; Prince, Sharon; Wang, Tao; Gao, Xiumei; Shi, Yujiang; Liu, Dali; Liu, Min; Wei, Wenyi; Wei, Zhi; Pan, Jingxuan; Wang, Yongjun; Xuan, Zhenyu; Hess, Jay; Hayward, Nicholas K.; Goding, Colin R.; Chen, Xiang; Zhou, Jun; Cui, Rutao.

In: Nature Communications, Vol. 9, No. 1, 259, 01.12.2018.

Research output: Contribution to journalArticle

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
Zhu, Bo ; Chen, Shuyang ; Wang, Hongshen ; Yin, Chengqian ; Han, Changpeng ; Peng, Cong ; Liu, Zhaoqian ; Wan, Lixin ; Zhang, Xiaoyang ; Zhang, Jie ; Lian, Christine G. ; Ma, Peilin ; Xu, Zhi Xiang ; Prince, Sharon ; Wang, Tao ; Gao, Xiumei ; Shi, Yujiang ; Liu, Dali ; Liu, Min ; Wei, Wenyi ; Wei, Zhi ; Pan, Jingxuan ; Wang, Yongjun ; Xuan, Zhenyu ; Hess, Jay ; Hayward, Nicholas K. ; Goding, Colin R. ; Chen, Xiang ; Zhou, Jun ; Cui, Rutao. / The protective role of DOT1L in UV-induced melanomagenesis. In: Nature Communications. 2018 ; Vol. 9, No. 1.
@article{c84ee669a6a84d35931ecc9a72b1bba8,
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",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41467-017-02687-7",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=85041386453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041386453&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-02687-7

DO - 10.1038/s41467-017-02687-7

M3 - Article

C2 - 29343685

AN - SCOPUS:85041386453

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 259

ER -