CENP-A Modifications on Ser68 and Lys124 Are Dispensable for Establishment, Maintenance, and Long-Term Function of Human Centromeres

Publication date: 9 January 2017
Source:Developmental Cell, Volume 40, Issue 1
Author(s): Daniele Fachinetti, Glennis A. Logsdon, Amira Abdullah, Evan B. Selzer, Don W. Cleveland, Ben E. Black
CENP-A is a histone H3 variant key to epigenetic specification of mammalian centromeres. Using transient overexpression of CENP-A mutants, two recent reports in Developmental Cell proposed essential centromere functions for post-translational modifications of human CENP-A. Phosphorylation at Ser68 was proposed to have an essential role in CENP-A deposition at centromeres. Blockage of ubiquitination at Lys124 was proposed to abrogate localization of CENP-A to the centromere. Following gene inactivation and replacement in human cells, we demonstrate that CENP-A mutants that cannot be phosphorylated at Ser68 or ubiquitinated at Lys124 assemble efficiently at centromeres during G1, mediate early events in centromere establishment at an ectopic chromosomal locus, and maintain centromere function indefinitely. Thus, neither Ser68 nor Lys124 post-translational modification is essential for long-term centromere identity, propagation, cell-cycle-dependent deposition, maintenance, function, or mediation of early steps in centromere establishment.

Teaser

CENP-A is a histone H3 variant important for centromere specification. In this Matters Arising article, using CENP-A gene replacement strategies, Fachinetti, Logsdon et al. provide evidence that the Ser68^phos and Lys124^ub modifications of CENP-A, previously proposed to regulate CENP-A function, are not required for long-term centromere identity, function, or maintenance.


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