Dynamic changes in CCAN organization through CENP-C during cell-cycle progression

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

show abstract

“…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%

“…In contrast, CENP-C has a web of interactions with other CCAN members, including CENP-A and CENP-H/-I/-K/-M (35,36,41) as well as outer kinetochore components (10,42). CENP-T/W/S/X also interacts both with CENP-H/-I/-K/-M (10) and the Ndc80 complex (13,43).…”

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.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The CENP-H group is located between the chromatin, CENP-C, and CENP-T-W-S-X. It plays roles in the maintenance and recruitment of CCAN Hori et al 2013;Basilico et al 2014;Nagpal et al 2015). The CENP-O group localizes to the kinetochore, downstream of the CENP-H group, and plays roles in microtubule dynamics and kinetochore alignment (Hori et al 2008b;Amaro et al 2010;Hua et al 2011;Eskat et al 2012;Bancroft et al 2015).…”

Section: The Inner Kinetochore Is Composed Of the Ccanmentioning

confidence: 99%

“…Recent studies suggest that there is no clear hierarchy for CCAN recruitment and maintenance (Hori et al 2008a;Fang et al 2015;McKinley et al 2015;Nagpal et al 2015), although there are active debates about this issue (Carroll et al 2010;Basilico et al 2014;Klare et al 2015). Various dynamic interactions between the different CCAN sub-complexes result in an extensive meshwork of interactions ( Fig.…”

Section: Cenp-c Functions Upstream Of Other Ccan Components During Dementioning

confidence: 99%

“…Various dynamic interactions between the different CCAN sub-complexes result in an extensive meshwork of interactions ( Fig. 3a) (Kwon et al 2007;Klare et al 2015;McKinley et al 2015;Nagpal et al 2015). This situation creates separate hierarchies during de novo CCAN recruitment and for maintenance of CCAN components at various cell cycle stages.…”

Section: Cenp-c Functions Upstream Of Other Ccan Components During Dementioning

confidence: 99%

See 1 more Smart Citation

Kinetochore assembly and function through the cell cycle

Nagpal

Fukagawa

2016

Chromosoma

Self Cite

View full text Add to dashboard Cite

The kinetochore is an essential structure for the chromosome segregation machinery in eukaryotes; it serves as a bridge between the spindle microtubules and chromosomes. The kinetochore consists of multiple interconnecting components on the centromere; therefore, understanding its formation, molecular function, and regulation has remained an ongoing challenge. Recent studies have provided new insights into centromere identity, kinetochore assembly, and function. In this review, we discuss recent advances in our understanding of the function and regulation of key kinetochore components. We highlight the reciprocal localization dependencies of the different sub-complexes of the kinetochore and describe their regulation during the cell cycle.

show abstract

Critical Foundation of the Kinetochore: The Constitutive Centromere-Associated Network (CCAN)

Hara

Fukagawa

2017

Progress in Molecular and Subcellular Biology

View full text Add to dashboard Cite

The kinetochore is a large protein complex, which is assembled at the centromere of a chromosome to ensure faithful chromosome segregation during M-phase. The centromere in most eukaryotes is epigenetically specified by DNA sequence-independent mechanisms. The constitutive centromere-associated network (CCAN) is a subcomplex in the kinetochore that localizes to the centromere throughout the cell cycle. The CCAN has interfaces bound to the centromeric chromatin and the spindle microtubule-binding complex; therefore, it functions as a foundation of kinetochore formation. Here, we summarize recent progress in our understanding of the structure and organization of the CCAN. We also discuss an additional role of the CCAN in the maintenance of centromere position and dynamic reorganization of the CCAN.

show abstract

Dynamic changes in CCAN organization through CENP-C during cell-cycle progression

Cited by 64 publications

References 35 publications

Stepwise unfolding supports a subunit model for vertebrate kinetochores

Stepwise unfolding supports a subunit model for vertebrate kinetochores

Kinetochore assembly and function through the cell cycle

Critical Foundation of the Kinetochore: The Constitutive Centromere-Associated Network (CCAN)

Contact Info

Product

Resources

About