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

Open Biology
Kathryn KixmoellerBen E Black

Abstract

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 ...Continue Reading

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Citations

Jul 29, 2020·Essays in Biochemistry·Ahmad Ali-Ahmad, Nikolina Sekulić
Feb 2, 2021·Science Advances·Na WangR Kelly Dawe
Mar 5, 2021·Journal of Molecular Recognition : JMR·Beibei CaoXiaojing He
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Feb 3, 2022·Current Opinion in Cell Biology·Midori Ishii, Bungo Akiyoshi

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Methods Mentioned

BETA
electron microscopy
X-ray

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