title: Centrosome dynamics as a source of chromosomal instability.
abstract: Accurate segregation of duplicated chromosomes between two daughter cells depends on bipolar spindle formation, a metaphase state in which sister kinetochores are attached to microtubules emanating from opposite spindle poles. To ensure bi-orientation, cells possess surveillance systems that safeguard against microtubule-kinetochore attachment defects, including the spindle assembly checkpoint and the error correction machinery. However, recent developments have identified centrosome dynamics--that is, centrosome disjunction and poleward movement of duplicated centrosomes--as a central target for deregulation of bi-orientation in cancer cells. In this review, we discuss novel insights into the mechanisms that underlie centrosome dynamics and discuss how these mechanisms are perturbed in cancer cells to drive chromosome mis-segregation and advance neoplastic transformation.
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Nam
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Naylor
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. Electronic address: vandeursen.jan@mayo.edu.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
mesh_terms: D000818:Animals; D002453:Cell Cycle; D018385:Centrosome / Q000378:metabolism* / Q000473:pathology; D043171:Chromosomal Instability / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics*; D006801:Humans; D018386:Kinetochores; D008677:Metaphase; D051379:Mice; D008870:Microtubules; D008938:Mitosis; D009369:Neoplasms / Q000473:pathology; D008941:Spindle Apparatus / Q000378:metabolism / Q000473:pathology
keywords: cancer; centrosome disjunction; centrosome dynamics; centrosome movement; chromosomal instability