title: Dido disruption leads to centrosome amplification and mitotic checkpoint defects compromising chromosome stability.
abstract: Numerical and/or structural centrosome abnormalities have been correlated with most solid tumors and hematological malignancies. Tumorigenesis also is linked to defects in the mitotic or spindle assembly checkpoint, a key control mechanism that ensures accurate segregation of chromosomes during mitosis. We have reported that targeted disruption of the Dido gene causes a transplantable myelodysplastic/myeloproliferative disease in mice. Here, we report that Dido3, the largest splice variant of the Dido gene, is a centrosome-associated protein whose disruption leads to supernumerary centrosomes, failure to maintain cellular mitotic arrest, and early degradation of the mitotic checkpoint protein BubR1. These aberrations result in enhanced aneuploidy in the Dido mutant cells. Dido gene malfunction thus is reported to be part of an impaired signaling cascade that results in a defective mitotic checkpoint, leading to chromosome instability.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Darwin 3, Campus de Cantoblanco, E-28049 Madrid, Spain. trachana@cnb.uam.es
authors.forename: Varvara
authors.initials: V
authors.lastname: Trachana
authors.forename: Karel H M
authors.initials: KH
authors.lastname: van Wely
authors.forename: Astrid Alonso
authors.initials: AA
authors.lastname: Guerrero
authors.forename: Agnes
authors.initials: A
authors.lastname: Fütterer
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
mesh_terms: D000818:Animals; D018385:Centrosome / Q000378:metabolism*; D043171:Chromosomal Instability; D048749:Cytokinesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D018390:Gene Targeting; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: C518584:DIDO1 protein, human; D004268:DNA-Binding Proteins; C120687:Dido protein, mouse; D014157:Transcription Factors; D014404:Tubulin