Ectopic Centromere Nucleation by CENP-A in Fission Yeast. Issue 4 (7th October 2014)

• Record Type: Journal Article
• Authors: Gonzalez, Marlyn; He, Haijin; Dong, Qianhua; Sun, Siyu; Li, Fei
• Is Part Of: Genetics. Volume 198:Issue 4(2014)
• Page Start: 1433
• Page End: 1446
• Publication Date: 2014-10-07
• Subjects: centromere -- CENP-A -- neocentromere -- heterochromatin -- epigenetics; Genetics -- Periodicals; 576.5
• DOI: 10.1534/genetics.114.171173
• Languages: English
• ISSNs: 0016-6731

Abstract

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-A Cnp1 in fission yeast results in the assembly of CENP-A Cnp1 at 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-A Cnp1 exhibit severe chromosome missegregation and spindle microtubule disorganization. In addition, pulse induction of CENP-A Cnp1 overexpression reveals that ectopic CENP-A chromatin can persist for multiple generations. Intriguingly, ectopic assembly of CENP-A cnp1 is suppressed by overexpression of histone H3 or H4. Finally, we demonstrate that deletion of the N-terminal domain of CENP-A cnp1 results 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 ubiquitin-dependent proteolysis. These studies expand our current understanding of how noncentromeric chromatin is protected from mistakenly assembling CENP-A.