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

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

Author information

1
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
2
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.
3
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
4
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
5
Genome Analysis Unit, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
6
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
7
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

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:

AT-rich DNA; Cse4/CENP-A; Mif2/CENP-C; budding yeast; centromere; nucleosome

PMID:
29074736
PMCID:
PMC5710141
DOI:
10.1101/gad.304782.117
[Indexed for MEDLINE]
Free PMC Article

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