Molecular Basis of CENP-C Association with the CENP-A Nucleosome at Yeast Centromeres

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2017 Oct 28

PMID 29074736

Citations 35

Authors

Hua Xiao

Feng Wang

Jan Wisniewski

Alexey K Shaytan

Rodolfo Ghirlando

Peter C FitzGerald

Yingzi Huang

Debbie Wei

Shipeng Li

David Landsman

Anna R Panchenko

Carl Wu

Affiliations

Soon will be listed here.

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.

Citing Articles

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Cai J, Quan Y, Zhang C, Wang Z, Hinshaw S, Zhou H Life Sci Alliance. 2024; 8(3.

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Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences.

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Binding to the Other Side: The AT-Hook DNA-Binding Domain Allows Nuclear Factors to Exploit the DNA Minor Groove.

Battista S, Fedele M, Secco L, Ingo A, Sgarra R, Manfioletti G Int J Mol Sci. 2024; 25(16).

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Concatemer Assisted Stoichiometry Analysis (CASA): targeted mass spectrometry for protein quantification.

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The cysteine-rich domain in CENP-A chaperone Scm3HJURP ensures centromere targeting and kinetochore integrity.

Folco H, Xiao H, Wheeler D, Feng H, Bai Y, Grewal S Nucleic Acids Res. 2023; 52(4):1688-1701.

PMID: 38084929 PMC: 10899784. DOI: 10.1093/nar/gkad1182.

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