Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Balcova, Izmir 35330, Turkey.
Université Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), 38000 Grenoble, France; Laboratoire de Biologie et de Modelisation de la Cellule (LBMC), CNRS/ENSL/UCBL, Ecole Normale Supérieure de Lyon, 69007 Lyon, France.
Trends Biochem Sci. 2023 Oct;48(10):849-859. doi: 10.1016/j.tibs.2023.07.010. Epub 2023 Aug 16.
CENP-A is an essential histone variant that replaces the canonical H3 at the centromeres and marks these regions epigenetically. The CENP-A nucleosome is the specific building block of centromeric chromatin, and it is recognized by CENP-C and CENP-N, two components of the constitutive centromere-associated network (CCAN), the first protein layer of the kinetochore. Recent proposals of the yeast and human (h)CCAN structures position the assembly on exposed DNA, suggesting an elusive spatiotemporal recognition. We summarize the data on the structural organization of the CENP-A nucleosome and the binding of CENP-C and CENP-N. The latter posits an apparent contradiction in engaging the CENP-A nucleosome versus the CCAN. We propose a reconciliatory model for the assembly of CCAN on centromeric chromatin.
着丝粒蛋白 A 是一种必需的组蛋白变体，可替代着丝粒处的典型 H3，并在表观遗传水平上标记这些区域。CENP-A 核小体是着丝粒染色质的特定构建块，它被着丝粒相关网络（CCAN）的两个组成部分 CENP-C 和 CENP-N 识别，CCAN 是动粒的第一层蛋白。酵母和人类（h）CCAN 结构的最新提议将组装定位于暴露的 DNA 上，这表明存在难以捉摸的时空识别。我们总结了关于 CENP-A 核小体的结构组织以及 CENP-C 和 CENP-N 结合的相关数据。后者提出了与 CCAN 结合时涉及 CENP-A 核小体的明显矛盾。我们提出了一个协调模型，用于在着丝粒染色质上组装 CCAN。
