Accurate mitosis requires the chromosomal passenger protein complex (CPC) containing Aurora B kinase, borealin, INCENP, and survivin, which orchestrates chromosome dynamics. However, the chromatin factors that specify the CPC to the centromere remain elusive. Here we show that borealin interacts directly with heterochromatin protein 1 (HP1) and that this interaction is mediated by an evolutionarily conserved PXVXL motif in the C-terminal borealin with the chromo shadow domain of HP1. This borealin-HP1 interaction recruits the CPC to the centromere and governs an activation of Aurora B kinase judged by phosphorylation of Ser-7 in CENP-A, a substrate of Aurora B. Consistently, modulation of the motif PXVXL leads to defects in CPC centromere targeting and aberrant Aurora B activity. On the other hand, the localization of the CPC in the midzone is independent of the borealin-HP1 interaction, demonstrating the spatial requirement of HP1 in CPC localization to the centromere. These findings reveal a previously unrecognized but direct link between HP1 and CPC localization in the centromere and illustrate the critical role of borealin-HP1 interaction in orchestrating an accurate cell division.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110276 | PMC |
http://dx.doi.org/10.1074/jbc.M114.572842 | DOI Listing |
Curr Opin Cell Biol
January 2025
Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan; Department of JFCR Cancer Biology, Institute of Science Tokyo, Tokyo, Japan. Electronic address:
Stable transmission of the genome during cell division is crucial for all life forms and is universally achieved by Aurora B-mediated error correction of the kinetochore-microtubule attachments. Aurora B is the enzymatic subunit of the tetrameric protein complex called the chromosomal passenger complex (CPC), and its centromeric enrichment is required for Aurora B to ensure accurate chromosome segregation. How cells enrich the CPC at centromeres is therefore an outstanding question to be elucidated.
View Article and Find Full Text PDFSci Rep
December 2024
CRBM CNRS UMR 5237, Equipe Cycle Cellulaire, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, France.
Accurate genome inheritance during cell division relies on a complex chromosome segregation mechanism. This process occurs once all the kinetochores of sister chromatids are attached to microtubules emanating from the opposite poles of the mitotic spindle. To control the precision of this mechanism, the Chromosome Passenger Complex (CPC) actively identifies and corrects improper microtubule attachments.
View Article and Find Full Text PDFCells
October 2024
Institute for Molecular Biology II, Center of Medical Biotechnology (ZMB), University of Duisburg-Essen, Universitätsstrasse 5, 45141 Essen, Germany.
bioRxiv
October 2024
Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104.
Pericentromeres are heterochromatic regions adjacent to centromeres that ensure accurate chromosome segregation. Despite their conserved function, they are composed of rapidly evolving A/T-rich satellite DNA. This paradoxical observation is partially resolved by epigenetic mechanisms that maintain heterochromatin, independent of specific DNA sequences.
View Article and Find Full Text PDFbioRxiv
July 2024
Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health; Bethesda, Maryland 20894, USA.
The primary constriction site of the M-phase chromosome is an established marker for the kinetochore position, often used to determine the karyotype of each species. Underlying this observation is the concept that the kinetochore is spatially linked with the pericentromere where sister-chromatids are most tightly cohered. Here, we found an unconventional pericentromere specification with sister chromatids mainly cohered at a chromosome end, spatially separated from the kinetochore in mouse oocytes.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!