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Mitotic kinase cascades orchestrating timely disjunction and movement of centrosomes maintain chromosomal stability and prevent cancer

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Abstract

Centrosomes are microtubule-organizing centers that duplicate in S phase to form bipolar spindles that separate duplicated chromosomes faithfully into two daughter cells during cell division. Recent studies show that proper timing of centrosome dynamics, the disjunction and movement of centrosomes, is tightly linked to spindle symmetry, correct microtubule-kinetochore attachment, and chromosome segregation. Here, we review mechanisms that regulate centrosome dynamics, with emphasis on the roles of key mitotic kinases in the proper timing of centrosome dynamics and how aberrancies in these processes may cause chromosomal instability and cancer.

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Abbreviations

Cdk1:

Cyclin-dependent kinase 1

Cep85:

Centrosome protein 85 KDa

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

GRK2:

G protein-coupled receptor kinase 2

Sav1:

Scaffold protein Salvador

KT:

Kinetochore

MEF:

Mouse embryonic fibroblast

Mst2:

Mammalian sterile 20-like kinase 2

NE:

Nuclear envelope

NEBD:

Nuclear envelope breakdown

Nek2A:

NIMA family kinase 2A

NIMA:

Never in Mitosis A

NPC:

Nuclear pore complex

PCM:

Pericentriolar material

Plk1:

Polo-like kinase 1

TEIF:

Transcriptional element-interacting factor

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Acknowledgments

This work was supported by grants from the National Institutes of Health (CA126828 and CA168709 to J.M.v.D.).

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Authors and Affiliations

  1. Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Janine H. van Ree, Hyun-Ja Nam & Jan M. van Deursen

  2. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Jan M. van Deursen

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  1. Janine H. van Ree
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  2. Hyun-Ja Nam
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  3. Jan M. van Deursen
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Correspondence to Jan M. van Deursen.

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Responsible Editor: Daniela Cimini and Giulia Guarguaglini

Janine H. van Ree and Hyun-Ja Nam shared first authors with equal contributions.

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van Ree, J.H., Nam, HJ. & van Deursen, J.M. Mitotic kinase cascades orchestrating timely disjunction and movement of centrosomes maintain chromosomal stability and prevent cancer. Chromosome Res 24, 67–76 (2016). https://doi.org/10.1007/s10577-015-9501-9

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