Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres
Open Access
- 1 October 2017
- journal article
- Published by Cold Spring Harbor Laboratory in Journal of Bone and Joint Surgery
- Vol. 31 (19), 1958-1972
- https://doi.org/10.1101/gad.304782.117
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.Keywords
Funding Information
- Center for Cancer Research
- National Cancer Institute
- National Library of Medicine
- National Institute of Diabetes and Digestive and Kidney Diseases
- Howard Hughes Medical Institute Janelia Research Campus
- Bloomberg Distinguished Professorship, Johns Hopkins University
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