European Molecular Biology Laboratory, 38042 Grenoble, France.
Department of Biochemistry, University of Colorado at Boulder, Boulder, CO 80309, USA.
Nucleic Acids Res. 2018 Nov 2;46(19):9907-9917. doi: 10.1093/nar/gky823.
Eukaryotic chromatin is a highly dynamic structure with essential roles in virtually all DNA-dependent cellular processes. Nucleosomes are a barrier to DNA access, and during DNA replication, they are disassembled ahead of the replication machinery (the replisome) and reassembled following its passage. The Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the replisome and deposits H3-H4 directly onto newly synthesized DNA. Therefore, CAF-1 is important for the establishment and propagation of chromatin structure. The molecular mechanism by which CAF-1 mediates H3-H4 deposition has remained unclear. However, recent studies have revealed new insights into the architecture and stoichiometry of the trimeric CAF-1 complex and how it interacts with and deposits H3-H4 onto substrate DNA. The CAF-1 trimer binds to a single H3-H4 dimer, which induces a conformational rearrangement in CAF-1 promoting its interaction with substrate DNA. Two CAF-1•H3-H4 complexes co-associate on nucleosome-free DNA depositing (H3-H4)2 tetramers in the first step of nucleosome assembly. Here, we review the progress made in our understanding of CAF-1 structure, mechanism of action, and how CAF-1 contributes to chromatin dynamics during DNA replication.
真核染色质是一种高度动态的结构，在几乎所有依赖于 DNA 的细胞过程中都具有重要作用。核小体是 DNA 进入的障碍，在 DNA 复制过程中，它们在复制机制（复制体）之前解体，并在其通过后重新组装。组蛋白伴侣染色质组装因子-1（CAF-1）与复制体相互作用，并将 H3-H4 直接沉积到新合成的 DNA 上。因此，CAF-1 对于建立和传播染色质结构非常重要。CAF-1 介导 H3-H4 沉积的分子机制仍不清楚。然而，最近的研究揭示了关于三聚体 CAF-1 复合物的结构和化学计量学以及它如何与底物 DNA 相互作用并将 H3-H4 沉积到其上的新见解。CAF-1 三聚体结合到单个 H3-H4 二聚体上，这诱导 CAF-1 发生构象重排，促进其与底物 DNA 的相互作用。两个 CAF-1·H3-H4 复合物在无核小体 DNA 上共缔合，在核小体组装的第一步中沉积（H3-H4）2 四聚体。在这里，我们回顾了我们在理解 CAF-1 结构、作用机制以及 CAF-1 如何在 DNA 复制过程中促进染色质动力学方面取得的进展。
