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Dev Cell. 2018 Nov 5;47(3):348-362.e7. doi: 10.1016/j.devcel.2018.09.003. Epub 2018 Oct 4.

Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP.

Author information

1
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
2
Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
3
Thermo Scientific, San Jose, CA 95134, USA.
4
Department of Biochemistry and Biophysics and Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
6
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: dfoltz@northwestern.edu.

Abstract

Centromeric chromatin defines the site of kinetochore formation and ensures faithful chromosome segregation. Centromeric identity is epigenetically specified by the incorporation of CENP-A nucleosomes. DNA replication presents a challenge for inheritance of centromeric identity because nucleosomes are removed to allow for replication fork progression. Despite this challenge, CENP-A nucleosomes are stably retained through S phase. We used BioID to identify proteins transiently associated with CENP-A during DNA replication. We found that during S phase, HJURP transiently associates with centromeres and binds to pre-existing CENP-A, suggesting a distinct role for HJURP in CENP-A retention. We demonstrate that HJURP is required for centromeric nucleosome inheritance during S phase. HJURP co-purifies with the MCM2-7 helicase complex and, together with the MCM2 subunit, binds CENP-A simultaneously. Therefore, pre-existing CENP-A nucleosomes require an S phase function of the HJURP chaperone and interaction with MCM2 to ensure faithful inheritance of centromere identity through DNA replication.

KEYWORDS:

DNA replication; centromere; chromatin; chromosome; epigenetics; helicase; mitosis; nucleosome

PMID:
30293838
PMCID:
PMC6219920
[Available on 2019-11-05]
DOI:
10.1016/j.devcel.2018.09.003

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