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酵母着丝粒处CENP-C与CENP-A核小体结合的分子基础。

Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres.

作者信息

Xiao Hua, Wang Feng, Wisniewski Jan, Shaytan Alexey K, Ghirlando Rodolfo, FitzGerald Peter C, Huang Yingzi, Wei Debbie, Li Shipeng, Landsman David, Panchenko Anna R, Wu Carl

机构信息

Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.

出版信息

Genes Dev. 2017 Oct 1;31(19):1958-1972. doi: 10.1101/gad.304782.117. Epub 2017 Oct 26.

DOI:10.1101/gad.304782.117
PMID:29074736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5710141/
Abstract

Histone CENP-A-containing nucleosomes play an important role in nucleating kinetochores at centromeres for chromosome segregation. However, the molecular mechanisms by which CENP-A nucleosomes engage with kinetochore proteins are not well understood. Here, we report the finding of a new function for the budding yeast Cse4/CENP-A histone-fold domain interacting with inner kinetochore protein Mif2/CENP-C. Strikingly, we also discovered that AT-rich centromere DNA has an important role for Mif2 recruitment. Mif2 contacts one side of the nucleosome dyad, engaging with both Cse4 residues and AT-rich nucleosomal DNA. Both interactions are directed by a contiguous DNA- and histone-binding domain (DHBD) harboring the conserved CENP-C motif, an AT hook, and RK clusters (clusters enriched for arginine-lysine residues). Human CENP-C has two related DHBDs that bind preferentially to DNA sequences of higher AT content. Our findings suggest that a DNA composition-based mechanism together with residues characteristic for the CENP-A histone variant contribute to the specification of centromere identity.

摘要

含有组蛋白CENP-A的核小体在着丝粒处形成动粒以进行染色体分离过程中发挥着重要作用。然而，CENP-A核小体与动粒蛋白相互作用的分子机制尚未完全清楚。在此，我们报道了出芽酵母Cse4/CENP-A组蛋白折叠结构域与动粒内部蛋白Mif2/CENP-C相互作用的新功能。令人惊讶的是，我们还发现富含AT的着丝粒DNA在Mif2招募中起重要作用。Mif2与核小体二分体的一侧接触，与Cse4残基和富含AT的核小体DNA都相互作用。这两种相互作用均由一个连续的DNA和组蛋白结合结构域（DHBD）介导，该结构域包含保守的CENP-C基序、一个AT钩和RK簇（富含精氨酸-赖氨酸残基的簇）。人类CENP-C有两个相关的DHBD，它们优先结合AT含量较高的DNA序列。我们的研究结果表明，基于DNA组成的机制以及CENP-A组蛋白变体的特征性残基有助于着丝粒身份的确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/14f1e5320ac1/1958f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/3f9c980d99ae/1958f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/fbebacf64c9e/1958f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/284cf330d917/1958f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/e59af597c615/1958f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/8114cb50b10c/1958f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/838c932f0605/1958f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/14f1e5320ac1/1958f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/3f9c980d99ae/1958f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/fbebacf64c9e/1958f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/284cf330d917/1958f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/e59af597c615/1958f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/8114cb50b10c/1958f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/838c932f0605/1958f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/260a/5710141/14f1e5320ac1/1958f07.jpg

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ETE 3: Reconstruction, Analysis, and Visualization of Phylogenomic Data.
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