Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP

Ewelina Zasadzińska, Jiehuan Huang, Aaron O. Bailey, Lucie Y. Guo, Nancy S. Lee, Shashank Srivastava, Kelvin A. Wong, Bradley T. French, Ben E. Black, Daniel R. Foltz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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. Inheritance of centromere identity requires the transmission of CENP-A across DNA replication, when nucleosomes are disassembled ahead of the replication fork. Zasadzińska et al. demonstrate that CENP-A requires the dedicated CENP-A chaperone HJURP and interaction with the replicative helicase complex to retain and redeposit CENP-A following DNA replication.

Original languageEnglish (US)
Pages (from-to)348-362.e7
JournalDevelopmental Cell
Volume47
Issue number3
DOIs
StatePublished - Nov 5 2018

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP'. Together they form a unique fingerprint.

Cite this