Propagation of centromeric chromatin requires exit from mitosis

J Cell Biol. 2007 Mar 12;176(6):795-805. doi: 10.1083/jcb.200701066. Epub 2007 Mar 5.

Abstract

Centromeres direct chromosomal inheritance by nucleating assembly of the kinetochore, a large multiprotein complex required for microtubule attachment during mitosis. Centromere identity in humans is epigenetically determined, with no DNA sequence either necessary or sufficient. A prime candidate for the epigenetic mark is assembly into centromeric chromatin of centromere protein A (CENP-A), a histone H3 variant found only at functional centromeres. A new covalent fluorescent pulse-chase labeling approach using SNAP tagging has now been developed and is used to demonstrate that CENP-A bound to a mature centromere is quantitatively and equally partitioned to sister centromeres generated during S phase, thereby remaining stably associated through multiple cell divisions. Loading of nascent CENP-A on the megabase domains of replicated centromere DNA is shown to require passage through mitosis but not microtubule attachment. Very surprisingly, assembly and stabilization of new CENP-A-containing nucleosomes is restricted exclusively to the subsequent G1 phase, demonstrating direct coupling between progression through mitosis and assembly/maturation of the next generation of centromeres.

Publication types

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

MeSH terms

  • Autoantigens / analysis
  • Autoantigens / metabolism*
  • Autoantigens / physiology
  • Centromere / metabolism*
  • Centromere / ultrastructure
  • Centromere Protein A
  • Chromatin / metabolism*
  • Chromatin / ultrastructure
  • Chromosomal Proteins, Non-Histone / analysis
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomal Proteins, Non-Histone / physiology
  • DNA Replication
  • Epigenesis, Genetic
  • G1 Phase / physiology
  • Humans
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Mitosis / physiology*
  • Models, Genetic
  • Recombinant Fusion Proteins / analysis

Substances

  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Recombinant Fusion Proteins