School of Biological Sciences, Nanyang Technology University, 60 Nanyang Drive, Singapore 637551, Singapore.
NTU Institute of Structural Biology, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921, Singapore.
Nucleic Acids Res. 2020 Jun 4;48(10):5383-5396. doi: 10.1093/nar/gkaa289.
Telomeres protect the ends of our chromosomes and are key to maintaining genomic integrity during cell division and differentiation. However, our knowledge of telomeric chromatin and nucleosome structure at the molecular level is limited. Here, we aimed to define the structure, dynamics as well as properties in solution of the human telomeric nucleosome. We first determined the 2.2 Å crystal structure of a human telomeric nucleosome core particle (NCP) containing 145 bp DNA, which revealed the same helical path for the DNA as well as symmetric stretching in both halves of the NCP as that of the 145 bp '601' NCP. In solution, the telomeric nucleosome exhibited a less stable and a markedly more dynamic structure compared to NCPs containing DNA positioning sequences. These observations provide molecular insights into how telomeric DNA forms nucleosomes and chromatin and advance our understanding of the unique biological role of telomeres.
端粒保护染色体的末端,是细胞分裂和分化过程中维持基因组完整性的关键。然而,我们对端粒染色质和核小体结构的分子水平了解有限。在这里,我们旨在定义人类端粒核小体的结构、动力学以及在溶液中的性质。我们首先确定了包含 145bp DNA 的人端粒核小体核心颗粒(NCP)的 2.2Å 晶体结构,该结构揭示了 DNA 的相同螺旋路径以及 NCP 两半的对称拉伸与 145bp '601' NCP 相同。在溶液中,与含有 DNA 定位序列的 NCP 相比,端粒核小体表现出较不稳定且明显更动态的结构。这些观察结果为端粒 DNA 如何形成核小体和染色质提供了分子见解,并增进了我们对端粒独特生物学功能的理解。