Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Centromere / metabolism
  • Centromere Protein A / genetics
  • Centromere Protein A / metabolism*
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly / physiology
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation / physiology
  • DNA Replication
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epigenomics
  • HEK293 Cells
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Kinetochores / metabolism
  • Mitosis / physiology
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • S Phase


  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HJURP protein, human
  • Histones
  • Nucleosomes