DOT1L and H3K79 Methylation in Transcription and Genomic Stability

Biomolecules - Tập 8 Số 1 - Trang 11
K Wood1,2, Michael Tellier3, Shona Murphy3
1Department of Biochemistry, University of Oxford, Oxford OX1 3RE, UK
2School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK
3Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK

Tóm tắt

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.

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