Aurora kinase B-phosphorylated HP1α functions in chromosomal instability

Monique M. Williams, Angela J. Mathison, Trent Christensen, Patricia T. Greipp, Darlene L. Knutson, Eric W. Klee, Michael T. Zimmermann, Juan Iovanna, Gwen A. Lomberk, Raul A. Urrutia

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1407-1421
Number of pages15
JournalCell Cycle
Volume18
Issue number12
DOIs
StatePublished - Jun 18 2019

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Keywords

  • Aurora Kinase
  • CBX5
  • chromosomal instability
  • HP1α

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Williams, M. M., Mathison, A. J., Christensen, T., Greipp, P. T., Knutson, D. L., Klee, E. W., Zimmermann, M. T., Iovanna, J., Lomberk, G. A., & Urrutia, R. A. (2019). Aurora kinase B-phosphorylated HP1α functions in chromosomal instability. Cell Cycle, 18(12), 1407-1421. https://doi.org/10.1080/15384101.2019.1618126