Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
Nucleic Acids Res. 2013 Mar 1;41(5):2797-806. doi: 10.1093/nar/gkt012. Epub 2013 Jan 23.
Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. Nuclear DNA is packaged into chromatin, and thus genome maintenance can be influenced by distinct chromatin environments. In particular, post-translational modifications of histones have emerged as key regulators of genomic integrity. Intense research during the past few years has revealed histone H4 lysine 20 methylation (H4K20me) as critically important for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction. The distinct H4K20 methylation states are mediated by SET8/PR-Set7 that catalyses monomethylation of H4K20, whereas SUV4-20H1 and SUV4-20H2 enzymes mediate further H4K20 methylation to H4K20me2 and H4K20me3. Disruption of these H4K20-specific histone methyltransferases leads to genomic instability, demonstrating the important functions of H4K20 methylation in genome maintenance. In this review, we explain molecular mechanisms underlying these defects and discuss novel ideas for furthering our understanding of genome maintenance in higher eukaryotes.
基因组完整性的维持对于确保正常的机体发育和预防癌症等疾病至关重要。核 DNA 被包装成染色质，因此基因组的维持可以受到不同染色质环境的影响。特别是组蛋白的翻译后修饰已成为基因组完整性的关键调节因子。在过去几年中，大量的研究揭示了组蛋白 H4 赖氨酸 20 位甲基化（H4K20me）对于确保基因组完整性的生物学过程（如 DNA 损伤修复、DNA 复制和染色质紧缩）至关重要。SET8/PR-Set7 催化 H4K20 的单甲基化，介导了不同的 H4K20 甲基化状态，而 SUV4-20H1 和 SUV4-20H2 酶则介导 H4K20 进一步甲基化为 H4K20me2 和 H4K20me3。这些 H4K20 特异性组蛋白甲基转移酶的破坏会导致基因组不稳定，这表明 H4K20 甲基化在基因组维持中的重要功能。在这篇综述中，我们解释了这些缺陷背后的分子机制，并讨论了进一步深入了解高等真核生物基因组维持的新想法。
