<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Disruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies"^^ . "Chromosomal instability (CIN) comprises an elevated rate of chromosome missegregation and correlates with the presence of extra centrosomes. Bipolar anaphases with clustered supernumerary centrosomes have been identified as a mechanism contributing to CIN via the formation of transient multipolar spindle intermediates, which promote merotelic kinetochore-microtubule attachment errors. \r\nHowever, the contribution of this model and that of potential additional mechanisms in human malignancies has not been addressed. \r\nHere we show that centriole rosettes, defined as multiple procentrioles engaged to a single parent, generate spindle asymmetry that favors kinetochore-microtubule attachment errors without centrosome clustering and ultimately results in CIN. Furthermore, we demonstrate that centriole rosettes, but not the progeny of clustered mitoses, are a common finding in primary human malignancies. \r\nCentriole rosettes are capable of arranging bipolar mitotic spindles but cause an increased frequency of anaphase lagging chromosomes and chromosome missegregation. The CIN phenotype is aggravated when spindle pole have asymmetric centriole numbers and it is not rescued by enhancement of kinetochore-microtubule attachment correction. \r\nFurthermore, by immunostaining for an array of centrosomal proteins, we find that, in primary human malignancies, centrosome amplification is characterized by supernumerary procentrioles forming rosettes around a single pair of parental centrioles, strongly arguing for a major contribution of this mechanism in the generation of CIN in vivo. \r\nOur results indicate that asymmetric centriole rosettes produce unbalanced microtubule numbers on mitotic half-spindles, thereby skewing the chance of binding microtubules from the more prominent spindle pole, resulting in impaired correction of merotelic kinetochore attachments and subsequent chromosome missegregation. We propose that centriole numbers at spindle poles must be carefully controlled to ensure chromosome segregation fidelity and disruption of this mechanism is an important source of CIN in human cancer. \r\n"^^ . "2015" . . . . . . . "Marco Raffaele"^^ . "Cosenza"^^ . "Marco Raffaele Cosenza"^^ . . . . . . "Disruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies (PDF)"^^ . . . "COSENZA - PhD THESIS 2015.pdf"^^ . . . "Disruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Disruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Disruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Disruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies (Other)"^^ . . . . . . "small.jpg"^^ . . . "Disruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #19144 \n\nDisruption of spindle pole symmetry by centriole overduplication induces chromosome instability in human malignancies\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .