Aurora kinase B-phosphorylated HP1α functions in chromosomal instability

ABSTRACT

Heterochromatin Protein 1 α (HP1α) associates with members of the chromosome passenger complex (CPC) during mitosis, at centromeres where it is required for full Aurora Kinase B (AURKB) activity. Conversely, recent reports have identified AURKB as the major kinase responsible for phosphorylation of HP1α at Serine 92 (S92) during mitosis. Thus, the current study was designed to better understand the functional role of this posttranslationally modified form of HP1α. We find that S92-phosphorylated HP1α is generated in cells at early prophase, localizes to centromeres, and associates with regulators of chromosome stability, such as Inner Centromere Protein, INCENP. In mouse embryonic fibroblasts, HP1α knockout alone or reconstituted with a non-phosphorylatable (S92A) HP1α mutant results in mitotic chromosomal instability characterized by the formation of anaphase/telophase chromatin bridges and micronuclei. These effects are rescued by exogenous expression of wild type HP1α or a phosphomimetic (S92D) variant. Thus, the results from the current study extend our knowledge of the role of HP1α in chromosomal stability during mitosis.

KEYWORDS:

• HP1α
• CBX5
• Aurora Kinase
• chromosomal instability

Author’s Contributions

GL and RU generated the main idea of the work and developed the study design, both conceptually and methodologically. MW, AM, TC, PG, and DK made significant contributions to the acquisition of data. EK, MZ and JI provided expertise for analysis and interpretation of data. MW, AM, RU and GL wrote the manuscript from first draft to completion. All authors read, made substantial comments, suggested appropriate modifications and corrections, and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary Material

Supplemental data for this article can be accessed here.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by National Institutes of Health Grants R01 CA178627 (to G.L.) and R01 DK52913 (to R.U.).