Ali-Ahmad Ahmad, Mors Mira, Carrer Manuel, Li Xinmeng, Bilokapić Silvija, Halić Mario, Cascella Michele, Sekulić Nikolina
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, University of Oslo, Oslo 0318, Norway.
Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern 0315, Norway.
bioRxiv. 2025 Jan 1:2024.12.31.630874. doi: 10.1101/2024.12.31.630874.
The centromere is a part of the chromosome that is essential for the even segregation of duplicated chromosomes during cell division. It is epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A associates specifically with a group of 16 proteins that form the centromere-associated network of proteins (CCAN). In mitosis, the kinetochore forms on the CCAN to connect the duplicated chromosomes to the microtubules protruding from the cell poles. Previous studies have shown that CENP-A replaces H3 in nucleosomes, and recently the structures of CENP-A-containing nucleosomes in complex with CCANs have been revealed, but they show only a limited interaction between CCANs and CENP-A. Here, we report the cryoEM structure of 2x(CENP-A/H4)-di-tetramers assembled on DNA in the absence of H2A/H2B histone dimer and speculate how (CENP-A/H4)-tetramers and -di-tetramers might serve as a platform for CCAN organization.
着丝粒是染色体的一部分，对于细胞分裂过程中复制染色体的均匀分离至关重要。它是由组蛋白H3变体CENP-A的存在表观遗传定义的。CENP-A与一组16种蛋白质特异性结合，这些蛋白质形成着丝粒相关蛋白质网络（CCAN）。在有丝分裂中，动粒在CCAN上形成，将复制的染色体连接到从细胞两极伸出的微管上。先前的研究表明，CENP-A在核小体中取代了H3，最近，与CCANs复合的含CENP-A核小体的结构已经被揭示，但它们只显示了CCANs和CENP-A之间有限的相互作用。在这里，我们报告了在没有H2A/H2B组蛋白二聚体的情况下在DNA上组装的2x（CENP-A/H4）-二聚体的冷冻电镜结构，并推测（CENP-A/H4）-四聚体和-二聚体如何作为CCAN组织的平台。
