Recognition of the centromere-binding protein Ndc10 by Scm3HJURP directs Cse4CENP-A deposition at native centromeres
- 1University of California, San Diego
Abstract
Kinetochores connect centromeres to spindle microtubules, ensuring accurate chromosome segregation. Kinetochore assembly at centromeres depends on deposition of CENP-A, a histone H3 variant. Despite considerable progress, how CENP-A is specifically assembled on native centromeres remains an open question. Centromere-specific assembly of CENP-A occurs spontaneously in a cell-free extract system from the yeast Saccharomyces cerevisiae, but with low efficiency, suggesting that one or more factors are limiting. Here, we show Scm3HJURP, a specific chaperone for the centromeric histone Cse4CENP-A, is one such limiting component. The addition of a complex of Scm3, Cse4 and histone H4 strongly stimulates Cse4 assembly in a centromeric DNA sequence- and dose-dependent manner; in addition, improvements in both Cse4 and kinetochore assembly were more prominent in mitotic versus interphase (G1) extracts. Using the complemented cell-free reconstitution system, we show that distinct Scm3 interfaces with Cse4 and with the Ndc10 subunit of the yeast centromere DNA sequence-recognizing CBF3 complex are essential for centromere-specific Cse4 assembly and cell viability. Thus, recognition of Ndc10 directs Scm3-dependent and locus-specific centromeric histone deposition.
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BibTeX
@misc{cai2026recognition,
title = {{Recognition of the centromere-binding protein Ndc10 by Scm3HJURP directs Cse4CENP-A deposition at native centromeres}},
author = {J. Cai and Z. Wang and L. Cheng and T. Xu and C. Y. Zhang and S. M. Hinshaw and R. T. Suhandynata and A. Desai and H. Zhou},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.763002},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763002v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Recognition of the centromere-binding protein Ndc10 by Scm3HJURP directs Cse4CENP-A deposition at native centromeres
AU - J. Cai
AU - Z. Wang
AU - L. Cheng
AU - T. Xu
AU - C. Y. Zhang
AU - S. M. Hinshaw
AU - R. T. Suhandynata
AU - A. Desai
AU - H. Zhou
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.763002
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.763002v1
AB - Kinetochores connect centromeres to spindle microtubules, ensuring accurate chromosome segregation. Kinetochore assembly at centromeres depends on deposition of CENP-A, a histone H3 variant. Despite considerable progress, how CENP-A is specifically assembled on native centromeres remains an open question. Centromere-specific assembly of CENP-A occurs spontaneously in a cell-free extract system from the yeast Saccharomyces cerevisiae, but with low efficiency, suggesting that one or more factors are limiting. Here, we show Scm3HJURP, a specific chaperone for the centromeric histone Cse4CENP-A, is one such limiting component. The addition of a complex of Scm3, Cse4 and histone H4 strongly stimulates Cse4 assembly in a centromeric DNA sequence- and dose-dependent manner; in addition, improvements in both Cse4 and kinetochore assembly were more prominent in mitotic versus interphase (G1) extracts. Using the complemented cell-free reconstitution system, we show that distinct Scm3 interfaces with Cse4 and with the Ndc10 subunit of the yeast centromere DNA sequence-recognizing CBF3 complex are essential for centromere-specific Cse4 assembly and cell viability. Thus, recognition of Ndc10 directs Scm3-dependent and locus-specific centromeric histone deposition.
ER -