DOT1L：通过 BRCA1 调控甲基化依赖的放化疗反应
DOT1L: orchestrating methylation-dependent radiotheRAPy responses via BRCA1.
机构信息
Department of Radiation Oncology, University of Texas Health and Science Center, San Antonio, TX 78229, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
出版信息
Trends Pharmacol Sci. 2024 Nov;45(11):955-957. doi: 10.1016/j.tips.2024.09.008. Epub 2024 Oct 9.
Abstract
Breast Cancer Type 1 Susceptibility Protein (BRCA)-1 existing in several functionally distinct complexes, promotes DNA repair of DNA double-strand breaks (DSBs). A recent study by Tang and colleagues identifies the lysine methyltransferase Disruptor of Telomeric Silencing 1-Like (DOT1L) involved in modifying Receptor-Associated Protein 80 (RAP80) to promote BRCA1-A complex localization and repair functions at DNA breaks. This study illuminates a potential therapeutic target for cancer radiotherapy.
摘要
乳腺癌易感蛋白 1（BRCA）-1 存在于几个功能不同的复合物中，可促进 DNA 双链断裂（DSBs）的修复。最近，Tang 及其同事的一项研究确定了赖氨酸甲基转移酶端粒沉默干扰因子 1 样（DOT1L），该酶参与修饰受体相关蛋白 80（RAP80），以促进 BRCA1-A 复合物在 DNA 断裂处的定位和修复功能。这项研究为癌症放射治疗提供了一个潜在的治疗靶点。
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本文引用的文献
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DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.DOT1L 介导的 RAP80 甲基化促进 BRCA1 募集以引发 DNA 修复。
Proc Natl Acad Sci U S A. 2024 Aug 27;121(35):e2320804121. doi: 10.1073/pnas.2320804121. Epub 2024 Aug 22.
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Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors.组蛋白甲基转移酶DOT1L作为实体瘤治疗中一个有前景的表观遗传靶点。
Front Genet. 2022 Apr 13;13:864612. doi: 10.3389/fgene.2022.864612. eCollection 2022.
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DOT1L Is a Novel Cancer Stem Cell Target for Triple-Negative Breast Cancer.DOT1L 是三阴性乳腺癌的新型癌症干细胞靶标。
Clin Cancer Res. 2022 May 2;28(9):1948-1965. doi: 10.1158/1078-0432.CCR-21-1299.
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Making Connections: Integrative Signaling Mechanisms Coordinate DNA Break Repair in Chromatin.建立联系：整合信号机制协调染色质中的DNA断裂修复
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The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia.DOT1L 抑制剂 pinometostat 可降低 H3K79 甲基化水平，并在成人急性白血病中有一定的临床活性。
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