Aurora kinase B-phosphorylated HP1? functions in chromosomal instability.

ABSTRACT: Heterochromatin Protein 1 ? (HP1?) 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 HP1? at Serine 92 (S92) during mitosis. Thus, the current study was designed to better understand the functional role of this posttranslationally modified form of HP1?. We find that S92-phosphorylated HP1? 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, HP1? knockout alone or reconstituted with a non-phosphorylatable (S92A) HP1? 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 HP1? or a phosphomimetic (S92D) variant. Thus, the results from the current study extend our knowledge of the role of HP1? in chromosomal stability during mitosis.

SUBMITTER: Williams MM 

PROVIDER: S-EPMC6592258 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature