Ectopic centromere nucleation by CENP-A in fission yeast

Marlyn Gonzalez, Haijin He, Qianhua Dong, Siyu Sun, Fei Li

Research output: Contribution to journalArticle

Abstract

The centromere is a specific chromosomal locus that organizes the assembly of the kinetochore. It plays a fundamental role in accurate chromosome segregation. In most eukaryotic organisms, each chromosome contains a single centromere the position and function of which are epigenetically specified. Occasionally, centromeres form at ectopic loci, which can be detrimental to the cell. However, the mechanisms that protect the cell against ectopic centromeres (neocentromeres) remain poorly understood. Centromere protein-A (CENP-A), a centromere-specific histone 3 (H3) variant, is found in all centromeres and is indispensable for centromere function. Here we report that the overexpression of CENP-ACnp1in fission yeast results in the assembly of CENP-ACnp1at noncentromeric chromatin during mitosis and meiosis. The noncentromeric CENP-A preferentially assembles near heterochromatin and is capable of recruiting kinetochore components. Consistent with this, cells overexpressing CENP-ACnp1exhibit severe chromosome missegregation and spindle microtubule disorganization. In addition, pulse induction of CENP-ACnp1overexpression reveals that ectopic CENP-A chromatin can persist for multiple generations. Intriguingly, ectopic assembly of CENP-Acnp1is suppressed by overexpression of histone H3 or H4. Finally, we demonstrate that deletion of the N-terminal domain of CENP-Acnp1results in an increase in the number of ectopic CENP-A sites and provide evidence that the N-terminal domain of CENP-A prevents CENP-A assembly at ectopic loci via the ubiquitindependent proteolysis. These studies expand our current understanding of how noncentromeric chromatin is protected from mistakenly assembling CENP-A.

Original languageEnglish (US)
Pages (from-to)1433-1446
Number of pages14
JournalGenetics
Volume198
Issue number4
DOIs
StatePublished - Dec 1 2014

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Schizosaccharomyces
Centromere
Histones
Chromatin
Kinetochores
Chromosomes
Chromosome Segregation
Heterochromatin
Meiosis
centromere protein A
Mitosis
Microtubules
Proteolysis

ASJC Scopus subject areas

  • Genetics

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Ectopic centromere nucleation by CENP-A in fission yeast. / Gonzalez, Marlyn; He, Haijin; Dong, Qianhua; Sun, Siyu; Li, Fei.

In: Genetics, Vol. 198, No. 4, 01.12.2014, p. 1433-1446.

Research output: Contribution to journalArticle

Gonzalez, M, He, H, Dong, Q, Sun, S & Li, F 2014, 'Ectopic centromere nucleation by CENP-A in fission yeast', Genetics, vol. 198, no. 4, pp. 1433-1446. https://doi.org/10.1534/genetics.114.171173
Gonzalez, Marlyn ; He, Haijin ; Dong, Qianhua ; Sun, Siyu ; Li, Fei. / Ectopic centromere nucleation by CENP-A in fission yeast. In: Genetics. 2014 ; Vol. 198, No. 4. pp. 1433-1446.
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