Propagation of centromeric chromatin requires exit from mitosis

Lars E T Jansen, Ben E. Black, Daniel R. Foltz, Don W. Cleveland*

*Corresponding author for this work

Research output: Contribution to journalArticle

400 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)795-805
Number of pages11
JournalJournal of Cell Biology
Volume176
Issue number6
DOIs
StatePublished - Mar 12 2007

ASJC Scopus subject areas

  • Cell Biology

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