title: Loss of ATRX leads to chromosome cohesion and congression defects.
abstract: Alpha thalassemia/mental retardation X linked (ATRX) is a switch/sucrose nonfermenting-type ATPase localized at pericentromeric heterochromatin in mouse and human cells. Human ATRX mutations give rise to mental retardation syndromes characterized by developmental delay, facial dysmorphisms, cognitive deficits, and microcephaly and the loss of ATRX in the mouse brain leads to reduced cortical size. We find that ATRX is required for normal mitotic progression in human cultured cells and in neuroprogenitors. Using live cell imaging, we show that the transition from prometaphase to metaphase is prolonged in ATRX-depleted cells and is accompanied by defective sister chromatid cohesion and congression at the metaphase plate. We also demonstrate that loss of ATRX in the embryonic mouse brain induces mitotic defects in neuroprogenitors in vivo with evidence of abnormal chromosome congression and segregation. These findings reveal that ATRX contributes to chromosome dynamics during mitosis and provide a possible cellular explanation for reduced cortical size and abnormal brain development associated with ATRX deficiency.
authors.affiliation: Department of Paediatrics, University of Western Ontario, London, Canada.
authors.forename: Kieran
authors.initials: K
authors.lastname: Ritchie
authors.forename: Claudia
authors.initials: C
authors.lastname: Seah
authors.forename: Jana
authors.initials: J
authors.lastname: Moulin
authors.forename: Christian
authors.initials: C
authors.lastname: Isaac
authors.forename: Frederick
authors.initials: F
authors.lastname: Dick
authors.forename: Nathalie G
authors.initials: NG
authors.lastname: Bérubé
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D002467:Cell Nucleus; D002875:Chromosomes / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D013234:Stem Cells; D000075924:X-linked Nuclear Protein
chemical_list: D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein