The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle

Abstract

<jats:p>Eukaryotic chromosome segregation relies upon specific connections from DNA to the microtubule-based spindle that forms at cell division. The chromosomal locus that directs this process is the centromere, where a structure called the kinetochore forms upon entry into mitosis. Recent crystallography and single-particle electron microscopy have provided unprecedented high-resolution views of the molecular complexes involved in this process. The centromere is epigenetically specified by nucleosomes harbouring a histone H3 variant, CENP-A, and we review recent progress on how it differentiates centromeric chromatin from the rest of the chromosome, the biochemical pathway that mediates its assembly and how two non-histone components of the centromere specifically recognize CENP-A nucleosomes. The core centromeric nucleosome complex (CCNC) is required to recruit a 16-subunit complex termed the constitutive centromere associated network (CCAN), and we highlight recent structures reported of the budding yeast CCAN. Finally, the structures of multiple modular sub-complexes of the kinetochore have been solved at near-atomic resolution, providing insight into how connections are made to the CCAN on one end and to the spindle microtubules on the other. One can now build molecular models from the DNA through to the physical connections to microtubules.</jats:p>

Surface structures consisting of chromatin fibers in isolated barley (Hordeum vulgare) chromosomes revealed by helium ion microscopy

“…However, at the centromeric region of the barley chromosome, the chromatin fibers exhibited narrow and parallel arrangement stretching to both chromosome arms with loosely compacted. The formation of narrow and parallel might cause by alignment of the kinetochore complex associates with CENP-A nucleosome at centromere for attachment with spindle fiber (Cleveland et al 2003;Kixmoeller et al 2020). The complex of kinetochore could connect with an opened conformation of chromatin.…”

The N-terminal Tail ofC. elegansCENP-A Interacts with KNL-2 and is Essential for Centromeric Chromatin Assembly

“…In most species, active centromeres are defined by the presence of CENP-A, a histone variant that replaces histone H3 in centromeric nucleosomes (Kixmoeller et al, 2020;Mitra et al, 2020). CENP-A provides the physical foundation for assembly of the kinetochore, a multiprotein complex mediating spindle microtubule attachment to chromosomes (Musacchio and Desai, 2017).…”

Unconventional kinetochore kinases KKT2 and KKT3 have unique centromere localization domains

“…A major open question concerning the biology of kinetoplastids is how these organisms assemble kinetochores specifically at centromeres using a unique set of kinetochore proteins. Studies in other eukaryotes have shown that constitutively localized kinetochore proteins (such as CENP-A and CENP-C) play crucial roles in kinetochore specification and assembly (French and Straight, 2017; Hamilton and Davis, 2020; Kixmoeller et al, 2020). Among the six proteins that constitutively localize at kinetochores in T. brucei (KKT2, KKT3, KKT4, KKT20, KKT22, and KKT23), we previously showed that KKT4 is important for recruiting KKT20 but not many other proteins including KKT2 and KKT3 (Llauró et al, 2018).…”