Markert Jonathan, Zhou Keda, Luger Karolin
Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA.
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Sci Adv. 2021 Oct 15;7(42):eabk2380. doi: 10.1126/sciadv.abk2380.
The adenosine 5′-triphosphate (ATP)–dependent chromatin remodeler SMARCAD1 acts on nucleosomes during DNA replication, repair, and transcription, but despite its implication in disease, information on its function and biochemical activities is scarce. Chromatin remodelers use the energy of ATP hydrolysis to slide nucleosomes, evict histones, or exchange histone variants. Here, we show that SMARCAD1 transfers the entire histone octamer from one DNA segment to another in an ATP-dependent manner but is also capable of de novo nucleosome assembly from histone octamer because of its ability to simultaneously bind all histones. We present a low-resolution cryo–electron microscopy structure of SMARCAD1 in complex with a nucleosome and show that the adenosine triphosphatase domains engage their substrate unlike any other chromatin remodeler. Our biochemical and structural data provide mechanistic insights into SMARCAD1-induced nucleosome disassembly and reassembly.
腺苷5'-三磷酸（ATP）依赖性染色质重塑因子SMARCAD1在DNA复制、修复和转录过程中作用于核小体，但尽管它与疾病有关，关于其功能和生化活性的信息却很少。染色质重塑因子利用ATP水解的能量来滑动核小体、驱逐组蛋白或交换组蛋白变体。在这里，我们表明SMARCAD1以ATP依赖的方式将整个组蛋白八聚体从一个DNA片段转移到另一个DNA片段，但由于其能够同时结合所有组蛋白，它也能够从组蛋白八聚体进行从头核小体组装。我们展示了SMARCAD1与核小体复合物的低分辨率冷冻电子显微镜结构，并表明腺苷三磷酸酶结构域与底物的结合方式不同于任何其他染色质重塑因子。我们的生化和结构数据为SMARCAD1诱导的核小体拆卸和重新组装提供了机制上的见解。
