title: Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.
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.
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, United States of America.|Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, E-08193, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Pampalona
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, United States of America.|Biocomplexity Institute of Virginia Tech, Blacksburg, VA 24061, United States of America.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Roscioli
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, United States of America.
authors.forename: William T
authors.initials: WT
authors.lastname: Silkworth
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, United States of America.
authors.forename: Brent
authors.initials: B
authors.lastname: Bowden
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, E-08193, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Genescà
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, E-08193, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Tusell
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, United States of America.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimini
mesh_terms: D000705:Anaphase / Q000502:physiology*; D002478:Cells, Cultured; D020090:Chromosome Segregation / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D042361:Mammary Glands, Human / Q000166:cytology* / Q000378:metabolism; D008870:Microtubules / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*