The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly

During cell division, interactions between microtubules and chromosomes are mediated by the kinetochore, a proteinaceous structure located at the primary constriction of chromosomes. In addition to the centromere histone centromere protein A (CENP-A), 15 other members of the constitutive centromere associated network (CCAN) participate in the formation of a chromatin-associated scaffold that supports kinetochore structure. We performed a targeted screen analyzing unfolded centrochromatin from CENP-depleted chromosomes. Our results revealed that CENP-C and CENP-S are critical for the stable folding of mitotic kinetochore chromatin. Multipeak fitting algorithms revealed the presence of an organized pattern of centrochromatin packing consistent with arrangement of CENP-A-containing nucleosomes into up to five chromatin "subunits"-each containing roughly 20-30 nucleosomes. These subunits could be either layers of a boustrophedon or small loops of centromeric chromatin.centromere | kinetochore | CENP-A | centrochromatin | boustrophedon

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“…Indeed, CENP-C is required to efficiently recruit both inner and outer kinetochore components during kinetochore assembly (34)(35)(36)(37).…”

Section: The Role Of Ccan Proteins In the Maintenance Of Kinetochorementioning

confidence: 99%

Stepwise unfolding supports a subunit model for vertebrate kinetochores

Vargiu

Макаров

Allan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…[17][18][19] CENP-C and CENP-T serve as a platform for recruitment of the KMN network through pathways that are not yet well understood. [20][21][22][23][24][25][26][27][28][29] From the CCAN components, CENP-N and CENP-C recognize CENP-A. [30][31][32] Depletion of CENP-N or CENP-C in human cells by RNA interference leads to decreased incorporation of new CENP-A at centromeres.…”

Section: Introductionmentioning

confidence: 99%

The distinct functions of CENP-C and CENP-T/W in centromere propagation and function inXenopusegg extracts

Krizaic

Williams

Sánchez

et al. 2015

Nucleus

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“…A histone H3 CATD chimera is recognized by HJURP and stably incorporated into centromeric chromatin (Black et al 2004;Bodor et al 2013). The importance of HJURP in centromere maintenance was confirmed by tethering LacI-HJURP fusion protein to Lac operators at ectopic chromosomal loci, which consequently assemble CENP-A and form largely functional kinetochores (Barnhart et al 2011;Hori et al 2013). In Drosophila, which lack an HJURP homolog, CAL1 assembles CENP-A CID nucleosomes in an extremely similar manner to HJURP in vertebrates .…”

Section: Hjurp: the Cenp-a Chaperonementioning

confidence: 88%

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Westhorpe

Straight

2014

Cold Spring Harb Perspect Biol

149

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A fundamental challenge for the survival of all organisms is maintaining the integrity of the genome in all cells. Cells must therefore segregate their replicated genome equally during each cell division. Eukaryotic organisms package their genome into a number of physically distinct chromosomes, which replicate during S phase and condense during prophase of mitosis to form paired sister chromatids. During mitosis, cells form a physical connection between each sister chromatid and microtubules of the mitotic spindle, which segregate one copy of each chromatid to each new daughter cell. The centromere is the DNA locus on each chromosome that creates the site of this connection. In this review, we present a brief history of centromere research and discuss our current knowledge of centromere establishment, maintenance, composition, structure, and function in mitosis.

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The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly

Abstract: Engineered kinetochores reveal distinct functions of the CCAN in recruiting CENP-A to the centromere and acting as a structural core to directly recruit kinetochore proteins.

Cited by 197 publications

References 50 publications

Stepwise unfolding supports a subunit model for vertebrate kinetochores

Stepwise unfolding supports a subunit model for vertebrate kinetochores

The distinct functions of CENP-C and CENP-T/W in centromere propagation and function inXenopusegg extracts

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

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