DOT1L is a melanocyte lineage specific caretaker tumor suppressor

发布时间 : 2017/04/10点击量:
报告题目:DOT1L is a melanocyte lineage specific caretaker tumor suppressor

报告人:Prof. Rutao Cui(崔儒涛),波士顿大学

时间:2017年4月10日(周一)上午10:00 -11:00

地点:金沙8888js官方一楼中厅

报告内容简介:
The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in leukemogenesis. Here we demonstrate that, in contrast to leukemia, DOT1L have protective role in melanoma development. Specifically, the DOT1L gene was found overlapping with one frequent deletion region and somatic missense mutations with deleterious effects occur at significantly higher frequency than expected by chance in human melanomas. Specific mutations inactivate DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOTL1, UVR-induced DNA damage is inefficiently repaired such that DOT1L loss promotes melanoma development in mice after exposure to ultraviolet radiation (UVR). Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 binding SIRT1 to deacetylate XPA in a precision complex in nucleotide excision repair (NER).

报告人简介:崔儒涛教授现为波士顿大学医学院药理与实验治疗学系教授,皮肤病学系教授,药理与实验治疗系副主任,黑色素瘤中心主任。通过使用临床标本、模式动物和细胞生物学研究,揭示黑色素产生的生物学过程及在黑色素瘤发生过程中的作用,这些研究对皮肤色素疾病的治疗和黑色素瘤的防治具有重要意义。在Cell、Cancer Discovery, Molecular Cell和Science Signaling等重要杂志上发表论文多篇。作为课题负责人,获得美国NIH/NCI RO1基金项目资助3项 、美国抗癌协会2项、美国国防部项目1项、黑色素瘤研究基金会1项、Harry Lloyd研究基金会1项、Elisa U. Pardee基金会1项,直接科研经费近1000万美元, 获2014年国家自然基金委海外及港澳学者合作研究项目资助。 获得美国专利2项, 是美国抗癌协会终身研究员。

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