DOT1L 和 H3K79 甲基化在转录和基因组稳定性中的作用。
DOT1L and H3K79 Methylation in Transcription and Genomic Stability.
机构信息
Department of Biochemistry, University of Oxford, Oxford OX1 3RE, UK.
School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK.
出版信息
Biomolecules. 2018 Feb 27;8(1):11. doi: 10.3390/biom8010011.
The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL)-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.
真核生物基因组的染色质组织为细胞完成转录、DNA 复制和修复 DNA 损伤等基本细胞功能带来了挑战。因此，一系列蛋白质修饰和/或读取染色质状态，以调节对染色体 DNA 的访问。酵母 Dot1 和哺乳动物同源物 DOT1L 是可以将多达三个甲基添加到组蛋白 H3 赖氨酸 79（H3K79）的甲基转移酶。H3K79 甲基化涉及多种过程，包括 RNA 聚合酶 II 的转录延伸、DNA 损伤反应和细胞周期检查点激活。DOT1L 也是治疗混合谱系白血病（MLL）重排白血病的重要药物靶点，其中 DOT1L 定位错误会促进异常转录激活。本综述总结了目前已知的 Dot1/DOT1L 和 H3K79 甲基化在转录和基因组稳定性中的作用。
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