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Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing

Author

Listed:
  • Dongqing Pan

    (Max Planck Institute of Molecular Physiology)

  • Kai Walstein

    (Max Planck Institute of Molecular Physiology)

  • Annika Take

    (Max Planck Institute of Molecular Physiology)

  • David Bier

    (Max Planck Institute of Molecular Physiology)

  • Nadine Kaiser

    (Max Planck Institute of Molecular Physiology)

  • Andrea Musacchio

    (Max Planck Institute of Molecular Physiology
    University Duisburg-Essen, Universitätsstrasse)

Abstract

Nucleosomes containing the histone H3 variant CENP-A are the epigenetic mark of centromeres, the kinetochore assembly sites required for chromosome segregation. HJURP is the CENP-A chaperone, which associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. How these proteins interact to promote CENP-A deposition remains poorly understood. Here we show that two repeats in human HJURP proposed to be functionally distinct are in fact interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it. HJURP binds CENP-A:H4 dimers, and therefore assembly of CENP-A:H4 tetramers must be performed by two Mis18αβ:M18BP1:HJURP complexes, or by the same complex in consecutive rounds. The Mis18α N-terminal tails blockade two identical HJURP-repeat binding sites near the Mis18αβ C-terminal helices. These were identified by photo-cross-linking experiments and mutated to separate Mis18 from HJURP centromere recruitment. Our results identify molecular underpinnings of eukaryotic chromosome inheritance and shed light on how centromeres license CENP-A deposition.

Suggested Citation

  • Dongqing Pan & Kai Walstein & Annika Take & David Bier & Nadine Kaiser & Andrea Musacchio, 2019. "Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12019-6
    DOI: 10.1038/s41467-019-12019-6
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