CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading

Pan, Dongqing; Klare, Kerstin; Petrovic, Arsen; Take, Annika; Walstein, Kai; Singh, Priyanka; Rondelet, Arnaud; Bird, Alexander W.; Musacchio, Andrea

doi:10.7554/elife.23352

Cited by 71 publications

(123 citation statements)

References 64 publications

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“…Mis18 forms oligomers in S. pombe and humans [360,361]. The Mis18 complex further interacts with M18BP1 (Mis18 binding protein 1, also known as Knl2) [356,357,358,362,363]. No Mis18BP1 has been identified in S. pombe , but two recently identified proteins, Mis19/Eic1 and Mis20/Eic2 may act as functional orthologs of M18BP1 in this organism [364,365].…”

Section: The Propagation Of Centromeric Chromatinmentioning

confidence: 99%

A Molecular View of Kinetochore Assembly and Function

Musacchio

Desai

2017

Biology

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484

589

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Kinetochores are large protein assemblies that connect chromosomes to microtubules of the mitotic and meiotic spindles in order to distribute the replicated genome from a mother cell to its daughters. Kinetochores also control feedback mechanisms responsible for the correction of incorrect microtubule attachments, and for the coordination of chromosome attachment with cell cycle progression. Finally, kinetochores contribute to their own preservation, across generations, at the specific chromosomal loci devoted to host them, the centromeres. They achieve this in most species by exploiting an epigenetic, DNA-sequence-independent mechanism; notable exceptions are budding yeasts where a specific sequence is associated with centromere function. In the last 15 years, extensive progress in the elucidation of the composition of the kinetochore and the identification of various physical and functional modules within its substructure has led to a much deeper molecular understanding of kinetochore organization and the origins of its functional output. Here, we provide a broad summary of this progress, focusing primarily on kinetochores of humans and budding yeast, while highlighting work from other models, and present important unresolved questions for future studies.

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Section: The Propagation Of Centromeric Chromatinmentioning

confidence: 99%

A Molecular View of Kinetochore Assembly and Function

Musacchio

Desai

2017

Biology

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484

589

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“…The Mis18 complex binds HJURP directly and is required for the recruitment of HJURP and new CENP-A to the centromere in G1-phase [38,46–50] (Figure 3a). The human Mis18 complex forms an oligomeric structure that includes Mis18α and Mis18β paralogs, and Mis18BP1 [51 •• ,52 •• ]. CENP-C has been shown to participate in recruiting the Mis18 complex proteins to the existing centromere; although, it is unclear whether this interaction fully accounts for Mis18 recruitment [53–55].…”

Section: Cell Cycle Control Of Centromere Inheritancementioning

confidence: 99%

“…Mis18BP1 and HJURP are the major targets of CDK phosphorylation in the CENP-A deposition pathway [51 •• ,52 •• ,59,62,63 •• ] (Figure 3a,b). The expression of Mis18BP1 containing mutations within the CDK phosphorylation sites leads to CENP-A loading in G2; however, the level of CENP-A deposited is much lower than that observed in G1 [51 •• ,59,63 •• ].…”

Section: Cell Cycle Control Of Centromere Inheritancementioning

confidence: 99%

“…The expression of Mis18BP1 containing mutations within the CDK phosphorylation sites leads to CENP-A loading in G2; however, the level of CENP-A deposited is much lower than that observed in G1 [51 •• ,59,63 •• ]. Phosphorylation of sites within the Mis18α/β binding domain in the amino terminus of Mis18BP1, specifically Thr40 and Ser110, inhibit the binding of the Mis18α/β heterohexamer [51 •• ,52 •• ] (Figure 3b), providing a molecular basis of the inhibition of CENP-A deposition by CDK1 phosphorylation of Mis18BP1. Phosphorylation of Thr653 also inhibits recruitment of the Mis18 complex to centromeres, but lies outside of the Mis18α/β interaction domain [63 •• ], suggesting there is more to be learned about how phosphorylation by CDK1 inhibits this complex.…”

Section: Cell Cycle Control Of Centromere Inheritancementioning

confidence: 99%

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Posttranslational mechanisms controlling centromere function and assembly

Srivastava

Zasadzińska

Foltz

2018

Current Opinion in Cell Biology

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Accurate chromosome segregation is critical to ensure the faithful inheritance of the genome during cell division. Human chromosomes distinguish the location of the centromere from general chromatin by the selective assembly of CENP-A containing nucleosomes at the active centromere. The location of centromeres in most higher eukaryotes is determined epigenetically, independent of DNA sequence. CENP-A containing centromeric chromatin provides the foundation for assembly of the kinetochore that mediates chromosome attachment to the microtubule spindle and controls cell cycle progression in mitosis. Here we review recent work demonstrating the role of posttranslational modifications on centromere function and CENP-A inheritance via the direct modification of the CENP-A nucleosome and pre-nucleosomal complexes, the modification of the CENP-A deposition machinery and the modification of histones within existing centromeres.

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“…In contrast, CDK activity regulates multiple components of the deposition machinery to inhibit CENP-A deposition until mitosis is completed. Mis18BP1 is a substrate for CDK1 phosphorylation, and modification of the protein disrupts the association of the protein with the Mis18 α / β hexamer (Pan et al 2017; Silva et al 2012; Spiller et al 2017). CDK1 also phosphorylates HJURP to inhibit CENP-A deposition (Muller et al 2014; Stankovic et al 2017).…”

Section: Cenp-a Posttranslational Modifications and Deposition At Cenmentioning

confidence: 99%

Posttranslational modifications of CENP-A: marks of distinction

Srivastava

Foltz

2018

Chromosoma

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Centromeres are specialized chromosome domain that serve as the site for kinetochore assembly and microtubule attachment during cell division, to ensure proper segregation of chromosomes. In higher eukaryotes, the identity of active centromeres is marked by the presence of CENP-A (centromeric protein-A), a histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a foundation for centromere assembly and function. The posttranslational modification (PTM) of histone proteins is a major mechanism regulating the function of chromatin. While a few CENP-A site-specific modifications are shared with histone H3, the majority are specific to CENP-A-containing nucleosomes, indicating that modification of these residues contribute to centromere-specific function. CENP-A undergoes posttranslational modifications including phosphorylation, acetylation, methylation, and ubiquitylation. Work from many laboratories have uncovered the importance of these CENP-A modifications in its deposition at centromeres, protein stability, and recruitment of the CCAN (constitutive centromere-associated network). Here, we discuss the PTMs of CENP-A and their biological relevance.

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CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading

Cited by 71 publications

References 64 publications

A Molecular View of Kinetochore Assembly and Function

A Molecular View of Kinetochore Assembly and Function

Posttranslational mechanisms controlling centromere function and assembly

Posttranslational modifications of CENP-A: marks of distinction

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