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Structural highlights
Function
CENPA_YEAST Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. Required for functional chromatin architecture at the yeast 2-micron circle partitioning locus and promotes equal plasmid segregation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
Publication Abstract from PubMed
Kinetochores mediate chromosome segregation during cell division. They assemble on centromeric nucleosomes and capture spindle microtubules. In budding yeast, a kinetochore links a single nucleosome, containing the histone variant Cse4(CENP-A) instead of H3, with a single microtubule. Conservation of most kinetochore components from yeast to metazoans suggests that the yeast kinetochore represents a module of the more complex metazoan arrangements. We describe here a streamlined protocol for reconstituting a yeast centromeric nucleosome and a systematic exploration of cryo-grid preparation. These developments allowed us to obtain a high-resolution cryoelectron microscopy reconstruction. As suggested by previous work, fewer base pairs are in tight association with the histone octamer than there are in canonical nucleosomes. Weak binding of the end DNA sequences may contribute to specific recognition by other inner kinetochore components. The centromeric nucleosome structure and the strategies we describe will facilitate studies of many other aspects of kinetochore assembly and chromatin biochemistry.
Cryoelectron Microscopy Structure of a Yeast Centromeric Nucleosome at 2.7 A Resolution.,Migl D, Kschonsak M, Arthur CP, Khin Y, Harrison SC, Ciferri C, Dimitrova YN Structure. 2020 Jan 29. pii: S0969-2126(19)30440-X. doi:, 10.1016/j.str.2019.12.002. PMID:32004465[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stoler S, Keith KC, Curnick KE, Fitzgerald-Hayes M. A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev. 1995 Mar 1;9(5):573-86. PMID:7698647
- ↑ Meluh PB, Yang P, Glowczewski L, Koshland D, Smith MM. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell. 1998 Sep 4;94(5):607-13. PMID:9741625
- ↑ Baker RE, Harris K, Zhang K. Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components. Genetics. 1998 May;149(1):73-85. PMID:9584087
- ↑ Keith KC, Baker RE, Chen Y, Harris K, Stoler S, Fitzgerald-Hayes M. Analysis of primary structural determinants that distinguish the centromere-specific function of histone variant Cse4p from histone H3. Mol Cell Biol. 1999 Sep;19(9):6130-9. PMID:10454560
- ↑ Keith KC, Fitzgerald-Hayes M. CSE4 genetically interacts with the Saccharomyces cerevisiae centromere DNA elements CDE I and CDE II but not CDE III. Implications for the path of the centromere dna around a cse4p variant nucleosome. Genetics. 2000 Nov;156(3):973-81. PMID:11063678
- ↑ Glowczewski L, Yang P, Kalashnikova T, Santisteban MS, Smith MM. Histone-histone interactions and centromere function. Mol Cell Biol. 2000 Aug;20(15):5700-11. PMID:10891506
- ↑ Tanaka T, Cosma MP, Wirth K, Nasmyth K. Identification of cohesin association sites at centromeres and along chromosome arms. Cell. 1999 Sep 17;98(6):847-58. PMID:10499801
- ↑ Biggins S, Bhalla N, Chang A, Smith DL, Murray AW. Genes involved in sister chromatid separation and segregation in the budding yeast Saccharomyces cerevisiae. Genetics. 2001 Oct;159(2):453-70. PMID:11606525
- ↑ Morey L, Barnes K, Chen Y, Fitzgerald-Hayes M, Baker RE. The histone fold domain of Cse4 is sufficient for CEN targeting and propagation of active centromeres in budding yeast. Eukaryot Cell. 2004 Dec;3(6):1533-43. PMID:15590827 doi:https://dx.doi.org/10.1128/EC.3.6.1533-1543.2004
- ↑ Collins KA, Castillo AR, Tatsutani SY, Biggins S. De novo kinetochore assembly requires the centromeric histone H3 variant. Mol Biol Cell. 2005 Dec;16(12):5649-60. Epub 2005 Oct 5. PMID:16207811 doi:https://dx.doi.org/10.1091/mbc.E05-08-0771
- ↑ Hajra S, Ghosh SK, Jayaram M. The centromere-specific histone variant Cse4p (CENP-A) is essential for functional chromatin architecture at the yeast 2-microm circle partitioning locus and promotes equal plasmid segregation. J Cell Biol. 2006 Sep 11;174(6):779-90. PMID:16966420 doi:https://dx.doi.org/jcb.200603042
- ↑ Migl D, Kschonsak M, Arthur CP, Khin Y, Harrison SC, Ciferri C, Dimitrova YN. Cryoelectron Microscopy Structure of a Yeast Centromeric Nucleosome at 2.7 A Resolution. Structure. 2020 Jan 29. pii: S0969-2126(19)30440-X. doi:, 10.1016/j.str.2019.12.002. PMID:32004465 doi:https://dx.doi.org/10.1016/j.str.2019.12.002
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