| 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
In eukaryotes, a variant of conventional histone H3 termed CenH3 epigenetically marks the centromere. The conserved CenH3 chaperone specifically recognizes CenH3 and is required for CenH3 deposition at the centromere. Recently, the structures of the chaperone/CenH3/H4 complexes have been determined for Homo sapiens (Hs) and the budding yeasts Saccharomyces cerevisiae (Sc) and Kluyveromyces lactis (Kl). Surprisingly, the three structures are very different, leading to different proposed structural bases for chaperone function. The question of which structural region of CenH3 provides the specificity determinant for the chaperone recognition is not fully answered. Here, we investigated these issues using solution NMR and site-directed mutagenesis. We discovered that, in contrast to previous findings, the structures of the Kl and Sc chaperone/CenH3/H4 complexes are actually very similar. This new finding reveals that both budding yeast and human chaperones use a similar structural region to block DNA from binding to the histones. Our mutational analyses further indicate that the N-terminal region of the CenH3alpha2 helix is sufficient for specific recognition by the chaperone for both budding yeast and human. Thus, our studies have identified conserved structural bases of how the chaperones recognize CenH3 and perform the chaperone function.
Identification of Functionally Conserved Regions in the Structure of the Chaperone/Cen H3/H4 Complex.,Hong J, Feng H, Zhou Z, Ghirlando R, Bai Y J Mol Biol. 2012 Nov 23. pii: S0022-2836(12)00893-5. doi:, 10.1016/j.jmb.2012.11.021. PMID:23178171[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ 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
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- ↑ 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
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- ↑ 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
- ↑ Hong J, Feng H, Zhou Z, Ghirlando R, Bai Y. Identification of Functionally Conserved Regions in the Structure of the Chaperone/Cen H3/H4 Complex. J Mol Biol. 2012 Nov 23. pii: S0022-2836(12)00893-5. doi:, 10.1016/j.jmb.2012.11.021. PMID:23178171 doi:https://dx.doi.org/10.1016/j.jmb.2012.11.021
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