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

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...

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Main Authors: Kathryn Kixmoeller, Praveen Kumar Allu, Ben E. Black
Format: Article
Language:English
Published: The Royal Society 2020-06-01
Series:Open Biology
Subjects:
Online Access:https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200051
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author Kathryn Kixmoeller
Praveen Kumar Allu
Ben E. Black
author_facet Kathryn Kixmoeller
Praveen Kumar Allu
Ben E. Black
author_sort Kathryn Kixmoeller
collection DOAJ
description 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.
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spelling doaj.art-0b60aab021644cdf95496a19953e02d52022-12-22T00:20:41ZengThe Royal SocietyOpen Biology2046-24412020-06-0110610.1098/rsob.200051200051The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindleKathryn KixmoellerPraveen Kumar AlluBen E. BlackEukaryotic 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200051centromerekinetochoremitosischromatinepigeneticsnucleosome
spellingShingle Kathryn Kixmoeller
Praveen Kumar Allu
Ben E. Black
The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle
Open Biology
centromere
kinetochore
mitosis
chromatin
epigenetics
nucleosome
title The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle
title_full The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle
title_fullStr The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle
title_full_unstemmed The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle
title_short The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle
title_sort centromere comes into focus from cenp a nucleosomes to kinetochore connections with the spindle
topic centromere
kinetochore
mitosis
chromatin
epigenetics
nucleosome
url https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200051
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