Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase
Pampalona Sala, Judit (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Roscioli, Emanuele (Virginia Polytechnic Institute and State University. Department of Biological Sciences)
Silkworth, William T. (Virginia Polytechnic Institute and State University. Department of Biological Sciences)
Bowden, Brent (Virginia Polytechnic Institute and State University. Department of Biological Sciences)
Genescà, Anna (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Tusell Padrós, Laura (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Cimini, Daniela (Virginia Polytechnic Institute and State University. Department of Biological Sciences)

Date:	2016
Abstract:	Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.
Grants:	European Commission 323216 Ministerio de Economía y Competitividad SAF2013-43801-P Ministerio de Sanidad y Consumo RD06/0020/1020 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-282 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-524 Agència de Gestió d'Ajuts Universitaris i de Recerca 2007/FIC-00642 Agència de Gestió d'Ajuts Universitaris i de Recerca 2008/BE1-00443
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 11, Issue 1 (January 2016) , art. e0147420, ISSN 1932-6203

DOI: 10.1371/journal.pone.0147420
PMID: 26784746

17 p, 3.4 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles