Günesdogan Ufuk, Jäckle Herbert, Herzig Alf
Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Elife. 2014 Sep 9;3:e02443. doi: 10.7554/eLife.02443.
Eukaryotes package DNA into nucleosomes that contain a core of histone proteins. During DNA replication, nucleosomes are disrupted and re-assembled with newly synthesized histones and DNA. Despite much progress, it is still unclear why higher eukaryotes contain multiple core histone genes, how chromatin assembly is controlled, and how these processes are coordinated with cell cycle progression. We used a histone null mutation of Drosophila melanogaster to show that histone supply levels, provided by a defined number of transgenic histone genes, regulate the length of S phase during the cell cycle. Lack of de novo histone supply not only extends S phase, but also causes a cell cycle arrest during G2 phase, and thus prevents cells from entering mitosis. Our results suggest a novel cell cycle surveillance mechanism that monitors nucleosome assembly without involving the DNA repair pathways and exerts its effect via suppression of CDC25 phosphatase String expression.
真核生物将DNA包装成含有组蛋白核心的核小体。在DNA复制过程中，核小体被破坏，并与新合成的组蛋白和DNA重新组装。尽管取得了很大进展，但目前仍不清楚为什么高等真核生物含有多个核心组蛋白基因，染色质组装是如何控制的，以及这些过程是如何与细胞周期进程协调的。我们利用果蝇的组蛋白无效突变来表明，由一定数量的转基因组蛋白基因提供的组蛋白供应水平，在细胞周期中调节S期的长度。缺乏从头合成的组蛋白供应不仅会延长S期，还会导致细胞在G2期停滞，从而阻止细胞进入有丝分裂。我们的结果提示了一种新的细胞周期监测机制，该机制在不涉及DNA修复途径的情况下监测核小体组装，并通过抑制CDC25磷酸酶String的表达发挥作用。
